The machinery of healthy vasoconstriction: an overview

Jana Pourová; Patrícia Dias; Milan Pour; Přemysl Mladěnka

doi:10.1007/s00424-025-03103-6

. 2025 Jul 11;477(9):1163–1189. doi: 10.1007/s00424-025-03103-6

The machinery of healthy vasoconstriction: an overview

Jana Pourová ^1,^✉, Patrícia Dias ^2,³, Milan Pour ⁴, Přemysl Mladěnka ¹

PMCID: PMC12420716 PMID: 40640430

Abstract

Tissue perfusion is acutely regulated by the changes in the vascular tone resulting in vasodilatation or vasoconstriction (there are also long-term changes in tissue perfusion, effectively accomplished by vascular remodeling). Even though vasodilatation predominates under physiological conditions, vasoconstriction represents an essential part of normal vascular physiology. The process of vasoconstriction is very complex, being influenced by many mediators, some of which are produced by the adjacent endothelial cells. The purpose of this review is to provide an overview of the machinery of vasoconstriction addressing the main components. First, the role of calcium is discussed including its intracellular and extracellular sources, its principal function in smooth muscle contraction machinery and mechanisms counteracting its effects. Subsequently, protein kinase C is included with its activation, effects and feedback. The role of RhoA/ROCK system is addressed in a similar way. The next section deals with the role of vascular endothelium-derived contracting factors and their effects on the adjacent smooth muscle cells. Finally, principal mechanisms of action of vasoconstrictive stimuli and myogenic tone are concisely discussed.

Keywords: Vasoconstriction, Calcium, PKC, RhoA/ROCK, EDCF

Introduction

The primary role of the vascular system, crucial for the whole-body homeostasis, is to secure the transport of blood and substances to organs and tissues. The blood arteries are well adapted for this purpose. Briefly, the vessels are composed of three layers: tunica intima, known also as endothelium, formed by a single layer of endothelial cells in direct contact with the blood. Then, the adjacent layer, tunica media, mainly composed of vascular smooth muscle (VSM) cells and elastic fibers. And, finally, tunica externa (adventitia) that contains fibroblasts, nerve endings and adipocytes (perivascular adipose tissue, PVAT). In many vascular beds, glycocalyx formed by extracellular polysaccharides is present on the luminal surface [68]. The vascular system is capable of quick adaption to immediate needs of the organism. In general, the blood flow depends on the viscosity of the blood, on the length and diameter of the vessel, and on the pressure gradient. To regulate the flow, very rapid and highly effective change in the diameter of the blood vessels by vasoconstriction or vasodilatation is crucial. The more abundant small (feed) arteries and arterioles play a fundamental role in this process in contrast to the less abundant large (conduit) arteries. In the regulation of the arterial diameter, the VSM cells are the effectors which change the vessel diameter. The VSM cells tightly collaborate with endothelium, perivascular nerves, and PVAT. The endothelial cells are particularly important because they not only sense signals from the blood, but also produce certain vasoactive substances and participate in the modulation and propagation of the membrane potential. The process is significantly influenced by the presence of the intercellular gap junctions, which facilitate the synchronization of ion concentrations and the membrane potentials of adjacent cells as well as the transport of small signaling molecules. The capillaries are the vessels of the smallest diameter and differ from the others in many aspects. The capillary wall does not contain the VSM cells and is formed by one layer of endothelial cells, basal membrane and the pericytes. Among other functions, the pericytes participate in the regulation of microvascular tone [299]. All vascular cells can be influenced by a number of factors such as the membrane potential, vasoactive substances including neurotransmitters, pH changes, and physical stimuli. For this purpose, the cells dispose of diverse sensors such as plasma membrane ion channels and G-protein coupled receptors and intracellular receptors.

In addition to their different diameters, the blood vessels differ substantially in several aspects. First, vascular receptor distribution is not homogenous. Different vessel types display different receptor profiles and different levels of expression [161]. Distribution of these receptors depends on the vessel size, type (artery, capillary, vein) and location (CNS, coronary, periphery). The same is true for particular receptor subtypes (e.g. in mice, the vasodilatation to acetylcholine in coronary vessels is mediated by M₃ and M₂ receptors, while in the cerebral vessels by the M₅ subtype [144, 301]). The resistance arteries, in contrast to the conduit arteries, display myogenic constriction (see Sect."Mechanical stimuli"). Second, the vessels fit the role of the corresponding tissue. While arteries in the skeletal muscles mainly secure adequate oxygen and nutrient supply during activity [75], the gut vessels form a part of the gut vascular barrier which facilitates the absorption of nutrients and protects against harm [29]. Accordingly, different mediators are produced in organ-specific way as was shown for endothelial cells [209]. By way of example, liver sinusoidal endothelial cells produce hepatocyte growth factor which promotes the hepatocyte survival and liver regeneration [151], while bone capillaries and VSM cells produce the bone morphogenic protein 2 that regulates bone formation [177]. Third, natural differences arise not only among species or specific vascular beds, but also between biological sexes [12, 123, 265]. The sex hormones and their receptors influence expression and activity of various ion channels including potassium [274, 311] and calcium [100, 240, 274, 277, 314] channels, maintenance of intracellular Ca²⁺ stores [74] (see Sect."SOCE"), and plasma membrane- [204, 272] and intracellular- [99, 160] ATPases. The differences in the regulation of the vascular tone represent one of the factors which determinate the differences in the incidence and course of cardiovascular diseases between sexes [265]. Notably, the menopause-related changes result also in changes in vascular signaling [154]. Fourth, other cell types come into play in a region-specific manner. In the CNS, the astrocytes play an important role in arterial tone regulation, and the same is true for microglia in the cerebral capillaries [53]. The brain pericytes participate in the neurovascular coupling that secures the local increase in the cerebral blood flow due to neuronal activity [87, 165]. The pericytes display several other functions, such as maintaining homeostasis in microcirculation, regulation of vascular growth and impact on immune function (for a review, see [2, 165, 299]). In the periphery, the myeloid cells have an impact on the vascular tone under hypoxia (reported in rats [196]) or inflammation (reported for inflammatory bowel disease [88]). In general, pathological conditions affect the vascular regulation, and reciprocally, the vascular dysregulation can lead to a dysfunction or even contribute to (or cause) a disease [13, 37, 273, 278].

The aim of this review is to summarize the machinery of vasoconstriction addressing its most important components in a comprehensive way. This topic is very broad and, in fact, other excellent reviews have been published [53, 90, 162, 225, 259, 276]. While the previous reviews often focused in a detail on a specific aspect, the primary goal of this paper is to demonstrate the complexity of the vascular contraction. The most important signaling pathways will be described, first on the level of the vascular smooth muscle, and then in orchestration with the endothelium. Finally, principal mechanisms of action of vasoactive stimuli will be discussed.

Vascular smooth muscle in vasoconstriction

The blood vessels are permanently under the influence of both vasoconstrictive and vasodilatory stimuli; the prevailing factor determines the outcome. The VSM cell contraction is based on the interaction between two contractile proteins, actin and myosin, in the presence of sufficient Ca²⁺ amount in the cytoplasm. There are two principal sources of Ca²⁺ ions: release from the sarcoplasmic reticulum (SR) and influx of extracellular Ca²⁺ from Ca²⁺ channels. The Ca²⁺ ions bind to a cytoplasm protein called calmodulin and the resultant complex (Ca²⁺-CaM) activates myosin light chain kinase (MLCK). The MLCK phosphorylates myosin light chain (MLC) at the MLC₂₀ subunit (Ser 19), allowing myosin to bind to actin, which initiates muscle contraction. Importantly, negative feedback mechanisms secure the transient nature of the responses evoked. At the intracellular level, a highly interconnected system of signaling pathways integrates various key structures.

Maintenance of the resting ion level ratios on both sides of the plasma membrane and resting membrane potential is secured by two important ATPases: Na⁺/K⁺-ATPase, and the plasma membrane Ca²⁺ ATPase (PMCA). The Na⁺/K⁺-ATPase is a protein, ubiquitously expressed in the plasma membranes of animal cells. The α₁ isoform of the Na⁺/K⁺-ATPase is ubiquitous and plays a „housekeeping “ role, other isoforms are tissue specific with spatially restricted distribution. In the VSM cells, the α₂ isoform was shown to be co-localized with the Na⁺/Ca²⁺ exchanger and with the K_ATP channels [76, 175, 176]. There are four subtypes of the PMCA, numbered from 1 to 4. The PMCA₁ is a ubiquitous „housekeeping“ isoform, while the other isoforms are tissue specific, with PMCA₄ having been reported in the VSM cells. The PMCA becomes activated upon binding of the Ca²⁺-CaM complex and has autoinhibitory properties [35]. Inside the VSM cells, transfer of Ca²⁺ ions between the stores in the SR and cytoplasm is most important. Transport from SR to cytoplasm is secured by the ryanodine receptor (RyR) and the inositol 1,4,5,-triphosphate receptor (IP₃R) channels. There are three types of the RyR channels, named RyR₁, RyR₂ and RyR₃ [145]. All three subtypes were found in the vascular smooth muscle [200], with a significant regional heterogeneity. The IP₃R channels have a high degree of sequence and structural homology with the RyR channels but the former are more frequently expressed. Similar to the RyR channels, there are three isoforms, IP₃R₁, IP₃R₂ and IP₃R₃. The IP₃R₁ type is highly expressed in VSM and is abundant also in the endothelial cells [69, 264]. On the other hand, the sacro/endoplasmic reticulum calcium ATPase (SERCA) on the membrane of the SR uptakes cytosolic Ca²⁺ and decreases available cytosolic Ca²⁺. The SERCA in the VSM cells is activated by NO, which is produced in the adjacent endothelium and diffuses to the VSM cells [1].

For the sake of clarity, the following text will deal with principal vasoconstrictive signaling pathways according to its main components: calcium ions, protein kinase C, and the RhoA/ROCK system.

Calcium ions

The Ca²⁺ ions are present in the extracellular space around the VSM cells, in their cytoplasm and in intracellular stores. There is a huge concentration gradient. In the resting state, the Ca²⁺ ion concentration outside the cell is ~ 2–3 mM, whereas it reaches approximately 100 nM [41, 98, 110] in the cytoplasm, ie. approx. twenty-thirty thousand times less. In the SR, calcium concentration may be subject to local deviations, because of uneven distribution of Ca²⁺-binding proteins. It is estimated to be 0.3–1 mM under the resting potential, several orders of magnitude higher than in the cytoplasm [41]. The movement of Ca²⁺ ions across membranes (i.e. from extracellular space or from the SR) results in a change in the plasma levels, which can be local or global, and sustained or transient (sparks) [5, 72, 110, 117, 233, 259]. Importantly, the local change means elevation of Ca²⁺ concentration just in the proximity of the Ca²⁺-sensitive cellular structures such as the big conductance calcium-activated K⁺ channels (BK_Ca). Colocalization of the participating components is important [259]. Due to K⁺ efflux, the membrane potential becomes more negative, which can result in vasodilatation. By contrast, a global increase in the cytosolic calcium concentration ([Ca²⁺]_c) triggers vasoconstriction (see Sect."Effects of Ca²⁺"). Last but not least, the changes in Ca²⁺ levels can also take the form of waves (see Sect."The Ca²⁺ feedback").

Intracellular Ca²⁺ sources

The SR is the main intracellular store of Ca²⁺ ions. This organelle is present in all types of the VSM cells and constitutes a larger proportion of the total cell volume in the large elastic arteries compared to their small counterparts [26, 162]. The capacity of the SR is enhanced by the presence of the Ca²⁺-binding proteins, such as calsequestrin, calreticulin or calnexin. Ca²⁺ ions are released from the SR via the the RyR and IP₃R channels. The Ca²⁺-induced Ca²⁺ release (CICR) is triggered at the concentration of Ca²⁺ ~ 3 µM [162] in the proximity of the SR. This amplification is an important component of calcium signaling; however, it may not be essential for vasoconstriction [89]. On the other hand, the CICR is extremely important for activating the BK_Ca channels and for the negative feedback after excessive depolarization and calcium increase (see Sect."The Ca²⁺ feedback") [5]. The CICR is promoted by the activators of RyR and IP₃R channels, and, surprisingly, also by cAMP [234]. The Mg²⁺ ions or procaine exert the opposite effect as well as an excessive amount of calcium (high micromolar concentrations) [276].

The Ca²⁺ can also enter other organelles, mainly the mitochondria and the lysosomes through specific structures, such as mitochondria-associated membranes (MAMs) [222]. Calcium up-take by other cell organelles comes into play if the Ca²⁺ concentration in their proximity is abnormally high (for mitochondria > ~ 5–10 μM). The stored Ca²⁺ can be effluxed back to the cytoplasm and modulate [Ca²⁺]_c. The mitochondrial Ca²⁺ buffering may become more important under pathological conditions, such as atherosclerosis [66].

Extracellular Ca²⁺ sources

Extracellular calcium ions enter the cells through either the voltage-gated (Ca_v) channels or most of the types of the transient receptor potential (TRP) channels. In the VSM cells, two types of the voltage-gated Ca_v channels (Ca_v3.x or T-type and Ca_v1.2 or L-type) and various TRP channel subtypes have been identified (TRPC_1/3/4/5/6, TRPV_1/2/3/4, TRPA₁, TRPM_4/8 and TRPP₁) (for a review, see [55] and [61]). The entry of extracellular Ca²⁺ occurs continuously as a part of the basal ion transfer. As the Ca²⁺ ions are concomitantly being removed from the cytoplasm into the intracellular stores (SERCA), and the Ca²⁺ efflux through the plasma membrane (PMCA, Na⁺/Ca²⁺ exchanger NCX) is operating, this basal ion transfer leaves the VSM cells in the resting state. The Ca_v channels open upon depolarization of the plasma membrane and are regarded as the principal source of Ca²⁺ for vasoconstriction. The TRP channels are activated by various stimuli according to the channel subtype, such as the binding of agonists to the G protein-coupled receptor (GPCR) of G_q-type, increased pressure and wall stress (greater than ~ 20%) causing myogenic depolarization (see Sect."Mechanical stimuli"), and thermal stimuli (see Sect."Thermal stimuli").

SOCE

The intracellular store Ca²⁺ depletion can result in extracellular Ca²⁺ influx called store-operated Ca²⁺ entry (SOCE) [214]. Substantial Ca²⁺ depletion is required for SOCE initiation, and constitutive Ca²⁺ leakage has no effect. However, inhibition of the Ca²⁺ re-uptake by SERCA is a sufficient stimulus in itself [214]. On the other hand, SOCE becomes fully activated before the SR is completely depleted which can be considered a safety mechanism against a complete loss of stored Ca²⁺. The SOCE is regulated by various proteins such as calmodulin and calcium-calmodulin-dependent protein kinase II (CaMKII) [20, 283]. While the primary purpose of SOCE is the refilling of the intracellular Ca²⁺ stores, it is also involved in other vascular processes such as permeability regulation, vascular repair, cell proliferation, and immune response [190]. The SOCE is operating not only in the VSM cells but also in the adjacent endothelium (see Sect."Endothelium in vasoconstriction"). The primary purpose of endothelial SOCE remains the same (e.i. refilling of the intracellular Ca²⁺ stores), but additional specific functions have been attributed including the role in the endothelial nitric oxide signaling and blood pressure control [48, 191], endothelial permeability [121, 256], endothelial oxidative stress response [38, 139, 185], and excitation-transcription coupling [24, 63, 226].

Two principal proteins are involved in SOCE—the stromal interaction molecule (STIM) within the SR cisternae, and Orai protein located on the plasma membrane. The STIM acts as a Ca²⁺ sensor in the SR [231]. Two homologues, STIM₁ and STIM₂, are known, and the STIM₁ seems to be the principal one in SOCE. Similarly, three types of the Orai protein have been described, with Orai₁ being the most important. First, due to Ca²⁺ depletion below certain threshold, the STIM oligomerizes in the SR membrane. Subsequently, the STIM translocates and interacts with the plasma membrane lipids (phosphatidylinositol 4,5-bisphosphate (PIP₂)), to activate the Orai proteins through protein–protein interaction. The four Orai₁ subunits form a Ca²⁺-release-activated Ca²⁺ channel (CRAC) for extracellular Ca²⁺ entry and several channels assemble into a cluster that forms the SR-plasma membrane nanojunctions [52, 59]. The Ca²⁺ current (I_CRAC) is a highly Ca²⁺-selective low-conductance current which can be terminated by intracellular Ca²⁺ ions. Surprisingly, IP₃R channels (i.e. important channels for Ca²⁺ depletion from the SR) modulate the STIM/Orai interaction [58]. In addition to the I_CRAC, the intracellular store Ca²⁺ depletion can result in store-operated (I_SOC) and I_CRAC-like currents with different electrophysiological properties. Regarding the I_SOC current, the Orai₁ mediated Ca²⁺ entry causes TRPC₁ channel incorporation into the plasma membrane in close apposition to Orai₁ enabling the TRPC₁ activation by the STIM₁ and providing another Ca²⁺ (and, possibly, also Na⁺) point of entry [166, 231, 296]. The TRPC₁ channels are the principal channels for the vascular I_SOC, but other channel subtypes (e.g. TRPC₄ and TRPC₅) also participate, at least in some vascular beds [6, 19, 93, 212, 300]. As regards the I_CRAC-like current, the Orai₁ and TRPC₁ channels (and possibly other TRPC channels) can assemble into a heteromeric channel with mixed properties between I_CRAC and I_SOC [190]. While the interactions among STIM₁, Orai₁ and TRPC₁ are considered principal in SOCE, additional options also exist, such as the STIM₁-mediated TRPC₁-based I_SOC in the native contractile VSMCs which was Orai₁-independent and involved interactions between protein kinase C (see Sect."Protein kinase C") and PIP₂ [172]. In endothelium, the NO production may be selectively coupled to Orai₁ via TRPC₄ [39] but not TRPC₁ channels [190, 249]. Different ways of intracellular Ca²⁺ store refilling can dominate according to species and vascular beds. Noteworthy, SOCE research can be strongly influenced by the use of freshly isolated or long-term cultured VSM cells [172]. In the former case, the native contractile cells display Ca²⁺ currents which correspond to the TRPC-based SOCE and low expression of the Orai₁ proteins. In contrast, the long-term cultured cells display a non-contractile phenotype with proliferative, migrative and growth characteristics and the Ca²⁺ entry corresponding rather to the I_CRAC [17, 21, 213]. In other words, it is crucial to define the cell phenotype when studying the vascular SOCE.

The dysregulation of SOCE plays an important role in the development of vascular alterations or even diseases including hypertension [23], pulmonary hypertension [36, 235] and atherosclerosis [47, 313]. Accordingly, the expression of STIM₁ and Orai₁ in human microcirculation (reported in mesenteric artery) increased with age and negatively correlated with impaired endothelium-dependent vasodilatation [57]. The CRAC channel activation was increased in aortas from stroke-prone spontaneously hypertensive rats compared to normotensive animals by mechanisms dependent on STIM₁ and Orai₁ activation [73]. The mutation in STIM₁ and Orai₁ is likely related to many diseases (for review, see [141]). The same may be true for modulators of SOCE such as IP₃R channels [108].

Effects of Ca²⁺

Membrane depolarization and global increase of the cytosol Ca²⁺ concentration initiate the vascular smooth muscle cell constriction. The constriction cascade is triggered if [Ca²⁺]_c in the VSM cells exceeds certain value (in the resting state, the global calcium concentration is approx. 100 nM, depolarization of the plasma membrane by ~ 15 mV from the resting potential elevates global Ca²⁺ levels to ~ 300–400 nM [98]). The Ca²⁺ ions act either in complex with the regulatory proteins (principally with calmodulin), or directly. The Ca²⁺-CaM complex changes the conformation of MLCK and thus activates this kinase [41, 101] with subsequent phosphorylation of MLC. Vasoconstriction is the result of the myosin-actin interaction. The Ca²⁺-CaM complex also activates phosphatidylinositol-4,5-bisphosphate 3-kinase (PI₃K) [247], which sets in motion the vasoconstrictive RhoA/ROCK system (see Sect."RhoA/ROCK system"). These principal events are supported by other pro-vasoconstrictive effects, such as the Ca²⁺-CaM complex binding to calponin [162] which prevents its binding to actin (actin can thus bind to myosin).

In parallel, the elevated [Ca²⁺]_c influences the ion transfer across membranes (both plasmatic and intracellular), which, in turn, can modify the membrane potential. The transfer of Ca²⁺ and K⁺ ions is the most important. The transfer of Ca²⁺ into the cytosol intensifies the [Ca²⁺]_c elevation while the K⁺ ions are principal for the membrane potential modification. On the SR, the Ca²⁺ ions activate the IP₃R and the RyR channels. To open the IP₃R channels, both Ca²⁺ and inositol trisphosphate (IP₃) are required (IP₃ concentration of 10 μM induced a rapid and huge Ca²⁺ release in the primary cultured rat aortic smooth muscle cells [304]). Subsequently, amplification of the Ca²⁺ signals through the Ca²⁺-induced Ca²⁺ release (CICR) is allowed [42, 91, 239, 264, 276]. The IP₃R [275] and the RyR channels are also opened by CaMKII which has been previously activated by the Ca²⁺-CaM complex [65, 91, 270]. Another complex, Ca²⁺-S100A1, activates the RyR and Ca_v1.2 channels. The Ca²⁺-S100A1 and the Ca²⁺-CaM complexes bind to the same site on the RyR receptors [298] but have opposite effects at higher Ca²⁺ concentrations (> 1 µM) [182]. Importantly, the Ca²⁺ ions display the effects only within certain concentrations. The RyR channels are activated at the Ca²⁺ concentration ranging roughly from hundreds of nM to units of μM with the amplification of the Ca²⁺ signal (CICR) [61, 91, 150, 276]. Similarly, the activity of the IP₃R channels is inhibited by an abnormally high Ca²⁺ level in their proximity [91, 275]. The channel inactivation likely results from presence of several distinct Ca²⁺ binding sites. The bell-shaped response to Ca²⁺ prevents excessive contraction, and is an important part of vascular physiology. Importantly, the IP₃R and the RyR channels cannot be understood as strictly pro-vasoconstrictive channels. The same channels participate in calcium sparks and CICR with only local elevations in the Ca²⁺ concentrations which result in a vasodilatory action (see Sect."The Ca²⁺ feedback").

On the plasma membrane, the Ca²⁺ ions temporarily inactivate the K_v channels [44], which contributes to its depolarization and maintaining the Ca_v channels in an open-state (latter, when depolarization reaches a certain value, the K_v channels are opened and return the plasma membrane to the resting membrane potential). In some vascular beds, the opening of the Cl_Ca channels with Cl⁻ efflux contributes to depolarization [147]. The Ca²⁺-CaM complex activates calcineurin (protein phosphatase 2B), which inhibits the K_ATP channels on the plasma membrane and hence also contributes to its depolarization [228]. Finally, the effects of Ca²⁺ on the vascular TRP channels are noteworthy [103, 149]. In vascular systems, TRPC₃, TRPC₆, TRPM₄, and TRPM₅ are activated by Ca²⁺ionts [28]. Depending on the channel subtype, the effects of the Ca²⁺ ions can result in channel stimulation or inhibition. In general, these effects are mediated directly by Ca²⁺ or (more frequently) involve the Ca²⁺-binding proteins with calmodulin being the most prominent one. The calmodulin-binding domains have been identified in the cytosolic regions of various TRP channels, and these sites can bind both the free-calmodulin and the Ca²⁺-CaM complex. The third mechanism, by which the Ca²⁺ ions influence the TRP channels is through the activation of phospholipase C with the hydrolysis of PIP₂, and the production of inositol 1,4,5-triphosphate and diacylglycerol. For most TRP channels, PIP₂ acts as a positive regulator, and the PIP₂ hydrolysis leads to channel desensitization [279]. The role of vascular TRP channels may differ among vascular beds and species.

The Ca²⁺ feedback

The mechanisms counteracting vasoconstriction are physiologically activated from certain [Ca²⁺]_c levels (approximately at higher micromolar range). Determination of the exact critical concentration is not trivial, however, its individual value in the proximity of a particular cellular structure is crucial. The underlying mechanism is based on the modulation of the ion channel status, on the recovery of [Ca²⁺]_c and the membrane potential to the resting state. The Ca²⁺ ions act either directly, or in complex with regulatory proteins. On the plasma membrane, the Ca²⁺ ions activate the BK_Ca channels with K⁺ efflux and the membrane potential becomes more negative (hyperpolarization) [118]. As a consequence, the voltage-gated Ca_v channels on the plasma membrane are indirectly inactivated, and the influx of extracellular Ca²⁺ prevented (in the vascular smooth muscle, the Ca_v3.2 channel subtype is prominent [95]). On the SR, the IP₃R and the RyR channels are also inactivated from certain [Ca²⁺]_c. Inhibition of these channels stops CICR [65, 91]. Inhibition of the RyR channels is mediated by the Ca²⁺-CaM complex. A similar effect is exhibited by another calcium-binding protein, sorcin [52]. The decrease of [Ca²⁺]_c to the resting values is secured by several mechanisms. The Ca²⁺-CaM complex activates plasma membrane calcium ATPase (PMCA) [35]. The Ca²⁺ ions activate the CaMKII which phosphorylates the regulatory protein phospholamban (Thr-17) and, in this way, the SERCA with Ca²⁺ re-uptake to the SR is activated [43]. Notably, a certain part of the cytosolic Ca²⁺ can be transferred to mitochondria (see Sect."Intracellular Ca²⁺ sources").

The negative feedback regulation of the vascular tone includes calcium sparks. These local sparks originate from the SR through the clusters of the RyR channels, and the signal is amplified by CICR. The calcium sparks cause a local elevation in the Ca²⁺ concentration (10–100 μM), and, paradoxically, result in vasodilatation in the resistance arteries. The sparks are self-limiting as maximal activity of the RyR channels is at Ca²⁺ concentration ~ 10 μM, and its further increase decreases the probability of their opening. On the other hand, the RyR channels are closed at Ca²⁺ concentration below ~ 100 nM [61, 276]. Local increase in Ca²⁺ leads to the activation of Ca²⁺ gated channels, including the BK_Ca channels, resulting in the K⁺ efflux. This efflux leads to plasma membrane hyperpolarization (more negative) and inactivation of the voltage-gated channels, including the Ca_v channels (the Ca_v1.2. channels are the principal source of extracellular Ca²⁺). The global [Ca²⁺]_c remains at resting level or decreases, giving rise to vasodilatation. Importantly, to function properly, the calcium sparks occur locally very close to the plasma membrane, and physical proximity of the SR and the BK_Ca and Ca_v channels is necessary [259]. Also importantly, consecutive calcium sparks can form a calcium wave, which is more likely to occur in the arterioles then in the arteries. If such a wave results in a global [Ca²⁺]_c elevation, vasoconstriction follows [5]. The calcium waves (intracellular or intercellular) can have oscillatory character (i.e. during vasomotion [189]).

The calcium feedback mechanisms vary across different vascular beds. There are differences between small arterioles and upstream bigger arteries [289], as well as regional differences among arterioles. As regard the latter, while the Ca²⁺ sparks generally support vasodilatation, the myogenic tone was promoted in isolated retinal arterioles (25–40 μm external diameter) [140]. In some vessels, the calcium sparks can open the Cl_Ca channels formed by the TMEM16A protein. In the VSM, the opening of these channels leads to Cl⁻ efflux from the cell and membrane depolarization [106, 147]. Up-regulation of the Cl_Ca channels was described under hypertension, and accounts, at least partially, for the endothelial dysfunction [170]. In general, the intracellular calcium handling is altered with aging and can be related to cardiovascular diseases [92].

The role of Ca²⁺ is summarized in Fig. 1.

Protein kinase C

Protein kinase C (PKC) is a widely distributed cytoplasmic serine/threonine kinase with many isoforms [7]. The isoforms differ in their dependence on Ca²⁺ during activation. While conventional cPKCs (α, β, γ) require Ca²⁺, diacylglycerol and phosphatidylserine to be activated, just diacylglycerol and phosphatidylserine are needed to activate the novel nPKCs (δ, ε, η, θ), and, finally, the atypical aPKCs are activated by phosphatidylserine itself. Expression of individual isoforms in the VSM cells differs among species [85], and the precise role of each isoform is not yet fully understood. In the human VSM, the PKC_α,PKC_β,PKC_δ,PKC_ε isoforms have been identified [85].

Activation of PKC

The principal way of the PKC activation in the VSM cells is the activation of the GPCR of the G_q-type, and the production of diacylglycerol (DAG) and IP₃. First, the GPCR of the G_q-type is activated by an agonist or due to mechanical stimulation [7, 180, 252]. This activation results in the dissociation of the α subunit of the G-protein followed by the activation of phospholipase C (PLC) which subsequently hydrolyses the membrane phospholipid PIP₂ to DAG and IP₃. Phospholipase D is activated in a similar way and hydrolyses phosphatidylcholine to DAG and choline. DAG and IP₃ are important second messengers involved in the PKC cascade. The lipophilic DAG is localized in the proximity of the plasma membrane, where the substance activates the PKC with the participation of phosphatidylserine and Ca²⁺ ions (conventional PKCs) [86]. This activation is a complex process and involves PKC phosphorylation by the PKC kinase and autophosphorylation followed by the translocation to the plasma membrane with the participation of annexins [51] and other proteins [230]. The molecules of IP₃ are water soluble and diffuse through the cytosol to the SR surface, where the IP₃R channels are activated with concomitant Ca²⁺ release [254]. Amplification of the Ca²⁺ signal (CICR) follows (see Sect."Effects of Ca²⁺"). Both DAG and IP₃ have additional effects, related to vasoconstriction. On the plasma membrane, the TRPC₆ channels are directly activated by DAG [237], and the TRPC₃ channels by IP₃ [255, 318]. Both channels mediate extracellular ion influx (primarily Ca²⁺, but also Na⁺) resulting in membrane depolarization with opening of the voltage-gated channels and [Ca²⁺]_c increase. The DAG can be converted by DAG lipase into arachidonic acid, which inactivates the myosin light chain phosphatase (MLCP) both directly (at micromolar concentrations), and via the activation of ROCK (see Sect."Activation of RhoA and ROCK") [10, 82]. IP₃ is rapidly cleaved by specific phosphatases to inositol 1,4-bisphosphate (IP₂) [285].

Other ways of PKC activation exist. The PIP₂ can be phosphorylated by PI₃K to yield another second messenger, phosphatidylinositol-3,4,5-triphosphate (PIP₃) which activates the PKC [251]. In addition, PI₃K contributes to the activation of the pro-vasoconstrictive RhoA/ROCK pathway (see Sect."Activation of RhoA and ROCK"). The PI₃K has already been mentioned—it is activated by the Ca²⁺-CaM (see Sect."Effects of Ca²⁺"). PKC can also be cleaved by the caspases, generating a catalytically active kinase domain, or activated by lipid cofactors such as ceramide or arachidonic acid, or through lipid-independent mechanisms, such as oxidative modifications or tyrosine nitration [257]. Direct activation of PKC can be induced by phorbol esters [130]. Noteworthy, the PKC activation is modulated by vasodilatory mediators produced by the adjacent endothelium as demonstrated for H₂O₂ [84], and in the case of PKCα [111] and PKC_ε [16] also for NO.

Effects of activated PKC

The active PKC displays multiple effects in the VSM cells through the phosphorylation of target structures [225]. In general, the kinase causes depolarization of the plasma membrane, rise of [Ca²⁺]_c, inactivation of MLCP and vasoconstriction. On the plasma membrane, effects on ion transfers are crucial. PKC activates the Ca_v1.2 channels both directly and indirectly via activated tyrosine kinase SRC (interestingly, the Ca_v1.2 channels can also be activated directly by PI₃K, which activates PKC (see Sect."Activation of PKC") [31, 251]), and inhibits the K⁺ channels, principally the BK_Ca [153, 186, 261] and K_v channels [30, 201], but also the K_ATP channels [224, 228, 243]. Via this mechanism, PKC promotes depolarization and secondarily increases the activity of the voltage-gated channels including Ca_v1.2. PKC also inhibits Na⁺/K⁺ ATPase [22] and activates the Na⁺/H⁺ exchanger [14, 15] with subsequent depolarization and alkalinization of the cytoplasm [297].

Inside the VSM cells, the PKC inhibits MLCP and hence prevents the dephosphorylation of myosin [236, 295]. The MLCP contains a phosphatase (PP1c) and myosin phosphatase target (MYPT1) subunits. Dissociation of the PP1c–MYPT1 complex causes MLCP inactivation. The activity of MLCP is regulated by two endogenous inhibitors, protein kinase C-dependent phosphatase inhibitor of 17 kDa (CPI-17) and phosphatase holoenzyme inhibitor (PHI-1, member of the CPI-17 family). In the MLCP inactivation, PKC participates in two ways: phosphorylation of MYPT1 and PKC/arachidonic acid-induced dissociation of the PP1c-MYPT1 complex [4, 82] or the activation of CPI-17, PHI-1 and arachidonic acid and dissociation of the PP1c–MYPT1 complex [4]. In addition to the MLCP inhibition, PKC inhibits soluble guanylate cyclase and thus cGMP formation, and NO-induced vasodilatation [122]. Last, PKC phosphorylates proteins that bind actin in their unphosphorylated forms, such as calponin and caldesmon [131]. Other kinases may also be involved in calponin phosphorylation [302]. Noteworthy, autophosphorylation of PKC is calponin-dependent [133]. Accordingly, calponin is able to activate PKC in vitro; the knock-down of the calponin gene inhibited the PKC-dependent contraction [120, 131, 132, 225].

The role of PKC in arterial contraction is more prominent in small resistance arteries compared to larger arteries, where other pathways like Rho/ROCK also play a significant role [135]. Alterations in the PKC activity are implied in the pathogenesis of a number of diseases including systemic and pulmonary hypertension, diabetic vasculopathy, atherosclerosis, vasospasm and many others (for reviews, see [184, 225]). The PKC inhibitors are widely used in basic research, and have also various clinical applications [156] including the vessel-related pathologies (in some cases with inconclusive results [50]).

The PKC feedback

Activation of PKC is usually regarded as supportive of vasoconstriction. However, the kinase regulates its own effects and ensures transient contraction. The active PKC inactivates the MLCK and phosphorylates MLC₂₀, which limits interaction between myosin and actin [7, 112]; activates PMCA on the plasma membrane and SERCA on the SR with decrease of [Ca²⁺]_c [162, 236]; and facilitates the dissociation of G_αi-GTP from adenylate cyclase, thereby terminating its inhibition [126]. Notably, the PLC is inactivated by protein kinases A and G which both mediate vasodilatation [197].

Additionally, the PKC may increase the synthesis of the GTPase-accelerating protein (GAP) [171], which is involved in the inactivation of the pro-vasoconstrictive RhoA-GTP (see Sect."Activation of RhoA and ROCK"). In the endothelial cells (see Sect."Endothelium in vasoconstriction"), the active PKC stimulates the production of vasodilatory NO [206] and the secretion of natriuretic peptide C [183]. The PKC might also activate the Na⁺/Ca²⁺ exchanger (NCX) [253], and inhibit the TRPC channels involved in SOCE [242], but evidence in the VSM is lacking.

The role of PKC is summarized in Figs. 2 and 3.

Fig. 2 — The role of protein kinase C (PKC) in the vascular smooth muscle (VSM) cell contraction. The activation of PKC occurs through the action of vasoconstrictors on the G protein-coupled receptor of the G_q type (G_qPCR) on the plasma membrane, or by mechanical stimulation of the “stretch-sensitive” receptors. Upon binding of an agonist to the G_qPCR, the G-protein α subunit dissociates and the activation of phospholipase C (PLC) takes place. Afterwards, PLC hydrolyses phosphatidylinositol bisphosphate (PIP₂) to two important second messengers, diacylglycerol (DAG) and inositol trisphosphate (IP₃). In a similar way, phospholipase D (PLD) is activated, giving rise to the hydrolysis of phosphatidylcholine (PC) to DAG and choline. Lipophilic DAG remains in the proximity of the plasma membrane, being responsible for the activation of PKC with the participation of phosphatidylserine (PS) and Ca²⁺ ions. PKC activation involves phosphorylation and autophosphorylation with subsequent translocation of PKC to the plasma membrane in a process, involving the participation of annexins (anxs). In parallel, IP₃ activates the IP₃Rs on the surface of the sarcoplasmic reticulum (SR) allowing Ca²⁺ efflux. IP₃ and DAG also activate the transient receptor potential canonical (TRPC) channels on the plasma membrane. The [Ca²⁺]_c elevation leads to the formation of the calcium-calmodulin (Ca²⁺-CaM) complex. The myosin light chain kinase (MLCK) becomes activated by the Ca²⁺-CaM complex resulting in subsequent phosphorylation of the myosin light chain (MLC) and initiation of contraction. The Ca²⁺-CaM complex also activates phosphatidylinositol-4,5-bisphosphate 3-kinase (PI₃K), an enzyme that phosphorylates PIP₂ to form another PKC activator, phosphatidylinositol trisphosphate (PIP₃). Other pathways leading to PKC activation include oxidation, acetylation, or nitration. Once activated, PKC: 1) inhibits the K⁺ channels on the plasma membrane leading to depolarization, 2) directly activates the Ca_v1.2 (L-type) calcium channels, 3) inhibits Na⁺/K⁺ ATPase, and 4) activates the Na⁺/H⁺ exchanger (NHE). Depolarization, Ca²⁺ influx and alkalinization of the cytosol promote contraction. In addition, PKC inhibits MLCP directly through the phosphorylation of MLCP, and indirectly through the phosphorylation of inhibitory proteins (CPI-17, PHI-1). PKC also phosphorylates proteins that bind actin in the unphosphorylated form (calponin, caldesmon), thereby allowing actin to bind myosin. PKC also inhibits soluble guanylate cyclase (sGC) and thus blocks the NO-induced vasodilatation. The effects of PKA are supported by parallel pro-vasoconstriction events: the Rho-associated protein kinase (ROCK) is activated by PI₃K. DAG is also converted into arachidonic acid (AA) by the DAG lipase, which inactivates the MLCP directly and via the activation of ROCK. AA can also be produced after the activation of phospholipase A₂ by the hydrolysis of phosphatidylethanolamine (PE). Other abbreviations: ADP, adenosine diphosphate; ATP, adenosine triphosphate; BK_Ca, large conductance calcium-activated K⁺ channels; CPI-17, the phosphopeptide C-kinase potentiated protein phosphatase-1 inhibitor; GTP, guanosine triphosphate; IP₂, inositol 1,4-bisphosphate; IP₃R, inositol trisphosphate receptors; K_ATP, ATP-dependent K⁺ channels; K_v, the voltage-gated K⁺ channels; MLC-P, myosin light chain phosphorylated; NCX, sodium/calcium exchanger; P, phosphate; ↑pH, increase in cytosolic pH; PHI-1, phosphatase holoenzyme inhibitor; PKA, protein kinase A; PKC, kinase C; PKG, protein kinase G; PMCA, plasma membrane calcium ATPase; RyR, ryanodine receptor; SERCA, sarco/endoplasmic reticulum calcium ATPase

Fig. 3 — The dual role of protein kinase C (PKC) in the vascular smooth muscle (VSM) cells. Despite giving rise to vasoconstriction, PKC also acts in the opposite way securing a transient contraction. Among the counteracting effects of PKC are: 1) the inactivation of the myosin light chain kinase (MLCK); 2) the activation of the plasma membrane calcium ATPase (PMCA) and sarco/endoplasmic reticulum calcium ATPase (SERCA), giving rise to a drop in [Ca²⁺]_c and 3) enabling of the dissociation of the G protein-coupled receptor of the G_i type (G_iPCR) from adenylate cyclase (AC), thereby terminating its inhibition. PKC also possibly enhances the synthesis of GTPase-activating protein (GAP), which is involved in the inactivation of RhoA-GTP. Other abbreviations: ADP, adenosine diphosphate; anxs, annexins; ATP, adenosine triphosphate; Ca²⁺-CaM, calcium-calmodulin complex; GTP, guanosine triphosphate; IP₃R, inositol trisphosphate receptors; MLC, myosin light chain; MLC-P, myosin light chain phosphorylated; MLCP, myosin light chain phosphatase; NCX, sodium/calcium exchanger; NHE, sodium/proton exchanger; RyR, ryanodine receptors; SR, sarcoplasmic reticulum

RhoA/ROCK system

RhoA (Ras homolog family member A) is a small cytoplasmic GTPase from the Ras superfamily. Evolutionarily, RhoA is one of the oldest Rho GTPases. The protein has multiple functions, including the regulation of transcription and cell division. In the VSM cells, RhoA is abundant and significantly involved in vasoconstriction. The principle of functioning of this GTPase is the same as that of other small GTPases. In its inactive state, it is found in the cytoplasm in the form of RhoA-GDP bound to guanine nucleotide dissociation inhibitor (GDI).

Activation of RhoA and ROCK

RhoA is activated through two main pathways. First, by an extracellular vasoconstrictor, where [Ca²⁺]_c is not necessarily increased. Second, by elevated [Ca²⁺]_c with activation of PI₃K by the Ca²⁺-CaM complex [198]. In the former case, an extracellular agonist binds GPCR of the G_12/13-type and causes the dissociation of the α subunit. The RhoA-GDP dissociates from GDI and moves to the plasma membrane [94, 271]. The RhoA-GDP is activated upon activation of the guanine nucleotide-exchange factor (GEF), which exchanges GDP for GTP to give the active RhoA-GTP. The amount of RhoA-GTP is regulated by GTPase-accelerating protein (GAP), which stimulates the GTPase activity of G-protein (the α subunit catalyzes its own inactivation). Another mode of regulation is the phosphorylation of GDI by vasodilatory protein kinases A and G, which stabilizes the inactive Rho-GDP-GDI complex [27, 164, 217]. Importantly, the RhoA-GTP binds to the cytoplasmic Rho-associated protein kinase (ROCK), which becomes activated. In accord with the initial RhoA activation, the ROCK activation can occur with or without significant increase in [Ca²⁺]_c [83]. RhoA-independent ways of ROCK activation, such as that initiated by arachidonic acid, also exist [10].

ROCK and its effects

ROCK is a widely distributed cytoplasmic serine/threonine kinase. It has two isoforms, ROCK₁ and ROCK₂. After activation, ROCK moves partially to the plasma membrane. In general, the kinase exhibits vasoconstrictive effects as a result of the phosphorylation of many substrates. In particular, it phosphorylates the MYPT1 subunit (Thr695 and Thr853); the phosphorylation inactivates the MLCP and thereby prevents dephosphorylation of MLC₂₀ [94, 179]. This is the most important effect of ROCK in the VSM cells, where the ROCK₂ plays a major role [288]. The same process occurs indirectly through the CPI-17 (Thr38) [134] and through activation of the zipper interacting protein kinase (ZIPK), which subsequently phosphorylates the MYPT1 subunit (Thr696 and Thr18/Ser19). Interestingly, the CPI-17 is activated by PKC as well (see Sect."Effects of activated PKC"). Additionally, ROCK directly phosphorylates MLC₂₀, which initiates muscle contraction [94, 179], and directly inactivates the K_v channels on the plasma membrane thus preventing its repolarization [169]. ROCK displays numerous other effects such as the phosphorylation of calponin [125], LIM kinases 1 and 2 [202, 258], ERM proteins (ezrin-radixin-moesin) [178] and mDia proteins (1 a 2) [49].

The RhoA/ROCK system influences the vessels also outside the VSM cells. Its inhibition increases NO release from the endothelial cells [148]. Inhibition of RhoA in the renal tubular epithelium may reduce the reabsorption of Na⁺ ions, which indirectly modifies the blood pressure [163]. In hypertension, the RhoA/ROCK system is implicated in the increase of the vascular stiffness via increased expression of vasoconstrictor proteins and increased peripheral resistance [107, 317]. Accordingly, a higher impact of the RhoA/ROCK has been reported in SHR in contrast to normotensive rats [115, 116]. The RhoA/ROCK activity is increased under vasospastic angina and cerebral vasospasm following subarachnoid hemorrhage, and the ROCK inhibitors such as fasudil have been shown to alleviate these spasms [146, 173].

The RhoA/ROCK feedback

Active ROCK inhibits its own activation by downregulating the GEF expression [33]. The ROCK inhibition decreases the secretion of acetylcholine [97] and increases the secretion of dopamine [303]. However, the latter effects have been reported outside the vascular system, and evidence for VSM is lacking.

The role of RhoA/ROCK is summarized in Fig. 4.

Endothelium in vasoconstriction

The endothelial cell monolayer, which separates VSM from the blood is localized in close proximity to the VSM. The monolayer is exposed to many chemical and physical stimuli. A sufficiently intense stimulus triggers the formation and release of endothelial vasoactive substances and/or changes in the membrane potential. Both have impact on the neighboring VSM and endothelial cells, and also act in an autocrine fashion. Intercellular gap junctions formed by connexins play an important role in transmitting the changes in the membrane potential and possibly some of the small signaling molecules such as Ca²⁺, IP₃ and small molecules < ~ 1 kDa [114, 188]. As regards the former, the movement of the calcium ions through the gap junctions can be slower than other calcium signaling pathways, and it is unclear to what extent this accounts for the intercellular communication. The gap junctions between the smooth muscle and endothelium (MEGJ) contribute to myoendothelial communication. Similarly, the gap junctions between the adjacent endothelial cells (EEGJ) mediate communication in the axial direction. The importance of the gap junctions increases with decreasing arterial diameter. Conversely, their number and cell-to-cell communication decrease with age, and the expression of particular connexins is altered during senescence [308]. Other factors such as hyperlipidemia [155] or smoking [218] can also affect endothelial connexin expression.

Depolarization of the endothelial cell membrane promotes vasoconstriction, whereas hyperpolarization promotes vasodilatation [129, 281, 290]. Vasoactive substances from the endothelium are divided into the endothelium-derived contracting factors (EDCFs), and the endothelium-derived relaxing factors (EDRFs). Importantly, the role of the endothelial Ca²⁺ ions is different from their role in the VSM cells. While a global increase of Ca²⁺ concentration in the VSM cells leads to vasoconstriction, inside the endothelial cells, calcium induces vasodilatation due to the production of EDRFs and induction of hyperpolarization. As the aim of this review is to summarize the machinery of vasoconstriction, the principal EDCFs will be described next.

Endothelium-derived contracting factors EDCFs

Endothelium produces EDCFs which influence the adjacent VSM and endothelial cells. The best known EDCF is endothelin-1, although vasoconstrictive prostanoids might be more important. The following sections provide information on endothelin-1, vasoconstrictive prostanoids, hydroxyeicosatetraenoic acids, and some other EDCFs.

Endothelin 1

Endothelin 1 (ET-1) is a small peptide (21 AK) synthesized from big-ET-1 by the endothelin converting enzymes (ECEs). The ET-1 acts through the GPCR receptors called ET_A and ET_B. Both are located on the plasma membrane of VSM, where the ET_A subtype dominates; the activation of the proteins gives rise to vasoconstriction. The ET_B receptors are also present on the endothelial cells, where they are linked to vasodilatation. Upon being released from the endothelial cells, ET-1 induces a biphasic response. First, a short-term drop in the blood pressure caused by the activation of the endothelial ET_B receptors of G_q and G_i types with rise in both NO and PGI₂ (prostacyclin) production occurs. The initial response is followed by vasoconstriction, mainly due to ET_A receptor activation on the VSM [267], mediated by at least two pathways: the receptor of the G_q type (PKC activation) and that of the G_12/13 type (RhoA/ROCK activation). The ET_B receptors on the smooth muscle are also involved in vasoconstriction.

Due to rapid elimination, the effects of ET-1 are mainly local [266]. Under physiological conditions, the amount of ET-1 is tightly regulated. Upon reaction with the endothelial ET_B receptors, ET-1 itself increases the production of NO, which inhibits ECEs [159]. Calcitonin gene-related peptide (CGRP) is another regulator, which promotes the dissociation of ET-1 from the ET_A receptor. The CGRP is produced by the perivascular sensory neurons and may act through the membrane receptor and βγ subunits of the G-protein [181]. The CGRP can be released by capsaicin through the TRPV₁ channel activation (reported in the rat mesenteric artery) [128]. In addition, the CGRP activates the K_v channels and plasma membrane hyperpolarization.

Under physiological state, pharmacological blockade of the endothelin receptors has a mild effect. The importance of ET-1 increases under hypoxia [220] and pathological conditions. Its constitutive production is increased in diabetic patients, who have elevated ET-1 plasma levels and develop hyperresponsiveness to its effects, which contributes to endothelial dysfunction [174]. In hypertensive patients, ET-1 increases the tone of the afferent and efferent glomerular arterioles, decreases glomerular filtration rate [142], exhibits proinflammatory and profibrotic effects, promotes vascular remodeling and increases ROS production [238]. However, ET-1 plasma level is not necessarily elevated in the hypertensive patients, perhaps due to efficient elimination [79]. The use of ET-1 antagonists in routine clinical practice has so far been limited by their adverse effects, such as peripheral edema and reproductive toxicity in animals. They have been applied to the treatment of pulmonary hypertension (ambrisentan, bosentan, macitentan) [54, 208] and hypertension (aprocitentan) [56]. Interestingly, ET-1 is also involved in the development of atherosclerosis, myocardial infarction and heart failure [119, 138]. Its role may be dual [138], and possible pharmacological intervention is not yet resolved.

Prostanoids causing vasoconstriction

For vasoconstriction, the endothelium-originated prostanoids that diffuse to the VSM cells are more important than those produced directly in the VSM cells. COX-1 is their main producer under physiological conditions, whereas the importance of up-regulated COX-2 increases under hypertension, diabetes and obesity [284, 305]. COX-2 expression also increases with age; contribution of a more intense shear friction during pulsatile blood flow is also possible [269]. The role of prostanoids varies depending on the species and vascular beds. Vasoconstrictive effects have so far been demonstrated for PGH₂ and its derivatives PGF_2α and thromboxane A₂ (TxA₂) [78, 268, 294]. The production of TxA₂ was classically associated only with platelets, but, under some conditions, it may also be produced in the endothelium, as described in the aorta of SHR [78]. On the VSM cells, these three prostanoids activate the GPCR of the G_q-type: FP (PGF_2α) and TP (TxA₂, PGH₂) [192, 305]. The resultant effects are determined by the interplay among the mediators present, especially between the vasoconstrictive TxA₂ and the vasodilatory PGI₂. Surprisingly, mediators such as PGI₂ or NO can give rise to vasoconstriction under some conditions [71, 78, 109] (see Sect."Endothelial vasoconstriction counteracting previous stimuli"). Last, isoprostanes (IsoPs) are prostaglandin-like compounds the levels of which are elevated in a number of diseases [227]. The IsoPs are produced by the free radical-catalyzed peroxidation of arachidonic acid independent of the COX [194]. The 15-F_2t-IsoP (also known as 8-isoPGF_2alfa) is a potent vasoconstrictor acting via the TP receptor in several vascular beds [105, 193]. The same substance also increases endothelin 1 release, induces VSM cell proliferation and may inhibit platelet aggregation [207].

Hydroxyeicosatetraenoic acids

The vasoconstriction caused by the hydroxyeicosatetraenoic acids such as the 20-HETE is worth mentioning. This eicosanoid is the metabolite of arachidonic acid produced by the CYP4A and CYP4F enzymes. It is another CYP metabolite of arachidonic acid in addition to the epoxyeicosatrienoic acids (EETs), but with opposite effect on the vessels. 20-HETE is a TP receptor agonist [70]. Its vasoconstrictive action is mediated by activation of PKC and ROCK [203, 221, 229]. On the plasma membrane, the Ca_v1.2 [309, 312] and TRPC₆ channels [113, 232] are activated, and the BK_Ca channels inhibited [319]. Even though 20-HETE is generally viewed as a vasoconstrictor, opposite effects were also reported in some vascular beds including rabbit kidney [34], bovine coronary [215], bovine pulmonary [310] and mice basilar [62] arteries. These effects were partially blocked by indomethacin, indicating an involvement of cyclooxygenase, and by the removal of endothelium. The vasodilatation was attributed to NO synthetized by the endothelial NO synthase (eNOS) and to PGI₂. The formation of the latter might have resulted from the increased release of arachidonic acid due to the elevation of [Ca²⁺]_c triggered by 20-HETE [62]. Despite this contradiction, 20-HETE is generally regarded as a factor contributing to vascular dysfunction, and the development of hypertension [104]. Noteworthy, 20-HETE is interlinked with the renin/angiotensin system. Angiotensin II induces 20-HETE synthesis and release. Reciprocally, 20-HETE increases angiotensin-converting enzyme (ACE) transcription in the endothelial cells [104]. The substance also eliminates the endothelial effects of insulin [157].

Other pro-vasoconstrictive factors

Obesity, insulin resistance and diabetes [174], hypertension and age are the key factors that promote endothelium-dependent (EDCF) vasoconstriction [18, 205, 280, 282]. This conclusion is supported by several studies. In obese sedentary mice, the microvascular dysfunction, inflammation and ROS production were observed [80]. In obese subjects and diabetics, the production of endothelial ET-1 was elevated [174]. In spontaneously hypertensive rats, the calcium handling dysfunction (higher expression of the IP₃R₂ channels and SERCA₃) and impaired endothelial calcium signaling were reported in the aortic endothelial cells [195, 291]. Change in endothelial [Ca²⁺]_c levels under hypertension is thus possible, but there is not a clear consensus. Both higher [262] and lower [287] calcium levels were found in the aortic endothelial cells from spontaneously hypertensive rats compared to normotensive controls. However, this discrepancy could be related to the methodological difference (fresh endothelial cells vs cultured cells). Ageing is linked to COX up-regulation and increased ROS levels [205], and to affected calcium signaling [92]. Vasoconstriction by EDCFs may be intensified under vitamin D deficiency [292, 293] which is more common in seniors. Endothelial dysfunction is also promoted by many indirect factors, such as increased arginase activity [246] or deficiency of tetrahydrobiopterin (BH₄, required for the production of NO) [3].

While the detailed course of pronounced vasoconstriction under obesity, diabetes, hypertension and ageing can differ from case to case, ROS production is increased under all these conditions. The COX is the main source of the endothelial ROS [262] (there are also other sources, including the monomeric eNOS, and the ROS are also generated in PVAT [286] [80]). The ROS are vasoactive in several ways. First, eNOS dimerization and NO formation is inhibited [67, 158]. Second, superoxide anions (O₂^.−) react with the NO present to form peroxynitrite (ONOO⁻) which is vasoactive. Its effects are concentration-dependent. While peroxynitrite at very low concentrations (1–10 nM) activates COX and elevates H₂O₂ levels, the prostacyclin synthase is inactivated by nitration and PGI₂ production decreased at 10–20 folder higher levels. Consequently, the PGE₂ and PGF_2α production predominates [77]. Its effects on platelet aggregation are also dual, and switch from anti-aggregatory to pro-aggregatory with higher peroxynitrite levels [247]. Third, under redox stress, when the cellular glutathione disulfide/glutathione ratio is high, the eNOS becomes uncoupled by glutathionylation, and produces superoxide [96]. Fourth, the ROS diffuse into the VSM cells, where they activate the COX and the production of vasoconstrictive prostanoids (see Sect."Prostanoids causing vasoconstriction") [244]. And, finally, an excessive ROS production dysregulates the Ca²⁺ signaling in general [199].

Endothelial vasoconstriction counteracting previous stimuli

Although vasodilatation physiologically predominates over vasoconstriction at normal resting tone, the counteracting mechanisms are triggered in parallel. The endothelium-derived contraction can be also triggered by a sudden or severe stretching of a vessel [127] (see Sect."Mechanical stimuli"). These negative feedbacks are very important for the integrated vascular function, and endothelium plays a crucial role. By way of example, the agonists of the endothelial GPCR of the G_q type, such as acetylcholine (receptor subtype depends on the vascular bed, e.g. the M₃ receptors predominate in coronary circulation, while the M₅ receptors predominate in CNS [144, 301]) or ATP (P₂Y receptors) primarily induce endothelium-dependent hyperpolarization (EDH) and vasodilatation. They also display counteracting effects, including the activation of the Ca²⁺ independent iPLA₂. The produced lysophospholipids open the store-operated Ca²⁺ channels, and the subsequent Ca²⁺ influx activates cPLA₂. Arachidonic acid is released and COX-derived EDCFs generated [281]. The formation of individual prostanoids depends on the availability of prostaglandin synthases (TxA₂ synthase for TxA₂) and their activities, which are significantly modulated by ROS (see Sect."Other pro-vasoconstrictive factors").

In general, the RhoA/ROCK pathway counteracts the NO vasodilatation [216]. This cascade decreases the activity of PKB which is the direct activator of eNOS by phosphorylation (Ser-1177) [307]. It enhances arginase activity and thereby limits the amount of L-arginine for NO synthesis [187]. Furthermore, increased activity of the arginases gives rise to eNOS-uncoupling and thus switches its activity from the production of NO to that of the superoxide [306]. Accordingly, increased activity of the endothelial RhoA/ROCK pathway is associated with endothelial dysfunction [245]. However, its physiological function is undisputable as the pathway participates in the mechanosensing [180] of the natural blood flow and of the vascular stretch resulting in pressure-induced (myogenic) response (see Sect."Mechanical stimuli"); and is necessary for the endothelial barrier integrity [219]. Notably, low concentrations of angiotensin II stimulate calcium sparks [11].

Under some (non-physiological) conditions, even some vasodilators exhibit vasoconstrictive effects. Under hypoxia, NO induces coronary artery contraction, which is sGC-dependent, but unrelated to cGMP. Cyclic inosine monophosphate (cIMP) is produced, and this effect is associated with the activation of ROCK [71, 109]. Analogously, PGI₂ may induce vasoconstriction, and its elevated levels were found in SHR together with elevated TxA₂ [78]. The IP receptors that physiologically mediate the PGI₂ vasodilatory effects are unlikely to be functional. In contrast, the TP receptors show elevated sensitivity to PGI₂ which results in vasoconstriction instead of vasodilatation [64]. Similarly, acidification of the endothelial and VSM cells surprisingly inhibits eNOS activity [25].

The role of the endothelium in vasoconstriction is summarized in Fig. 5.

Vasoconstrictive stimuli

The endothelium and the VSM cells sense vasoactive stimuli. The interplay between them modifies the membrane potential and the traffic of Ca²⁺ ions, which are decisive for the smooth muscle response. The following sections deals with principal vasoconstrictive stimuli and their effects. According to origin, these stimuli can be divided into physical and chemical. The physical stimuli can be categorized as mechanical and thermal.

Mechanical stimuli

The mechanical stimuli are always in operation, even under the resting conditions as a result of the blood flow and physiological intravascular pressure. Physiologically, vasodilatation prevails over vasoconstriction due to the fluid shear stress and pulsatile stretch of the vascular wall with stimulation of NO production. In small arteries, elevated intraluminal pressure results in myogenic response, which contributes to the basal vascular tone and is important for the autoregulation of the blood flow. In mouse small mesenteric and renal arteries ex vivo, this response was observed after the elevation of the intraluminal pressure above 60 mmHg [248]. The myogenic response starts with the detection of the vascular wall stress. The mechanosensing is likely secured in multiple ways, and there are several candidates the mechanosensors, such as some GPCR and TRP channels. The AT₁ receptors were reported to be mechanosensitive, first in the cardiomyocytes [320] and leter in other vascular beds, such as murine mesenteric or renal arteries [248]. The essential involvement of the AT_1a receptor subtype was found in the same study. The activation of the AT₁ receptors triggers the G_q/PLC/IP₃ + DAG/PKC cascade (see Sect."Protein kinase C") [46]. Various TRP channels (formerly referred to as the stretch-activated channels, SACs) are involved in the myogenic response. However, there is little evidence supporting their direct activation by stretching in most cases, and the TRP channels can be rather viewed as the downstream members of the myogenic response. For example, the TRPC₆ channels are activated downstream of the mechanosensitive GPCR including the AT₁ [180]. Similar results were found for the TRPM₄ [211] and TRPV₁ [210] channels. On the other hand, the TRPP₁ [241] and TRPV₄ channels [260] may be mechanosensitive when associated with other proteins, but more experiments are needed to unravel their role. The endothelial TRPC₆ channels were also found to be mechanosensitive, but the results were obtained on cultured cells [315]. Last, the membrane glycoproteins-integrins [168] and the platelet endothelial cell adhesion molecule PECAM-1 [124] can also be involved. After mechanosensing, the plasma membrane is depolarized which leads to the opening of the Ca_v1.2. channels and Ca²⁺ influx. Elevation of [Ca²⁺]_c triggers vasoconstriction [136]. The transient response is secured by negative feedback mechanisms with the return of the membrane potential and [Ca²⁺]_c to the resting values (see Sect."The Ca²⁺ feedback"). The adipose-derived relaxing factor from PVAT may also participate in the tone regulation [81, 263]. There are obvious differences among specific arterial beds, for example, the myogenic response is more pronounced in the cerebral arteries than in the mesenteric arteries [143]. Other factors, such as species, age [45], and general health state have also an impact. An impairment in the myogenic response can be related to the progression of many diseases including diabetes [137, 250], heart failure [152] and stroke [40]. While the myogenic tone caused by fluid shear stress is an important part of vascular physiology, the same is not true for strong vessel stretching resulting from high arterial pressure. High arterial pressure can induce vascular smooth muscle hypertrophy and hyperplasia with changes in the contractile and matrix proteins and is involved in vascular pathologies [8]. Notably, cardiac pulsation can generate circumferential stretch [32] which leads to angiotensin II release from the endothelium and the elevation of superoxide levels [167], the superoxide may thus be involved in the signaling pathways. The effects on health can be both positive and negative [8, 9, 102].

Thermal stimuli

If the temperature drops under a certain level, the organism responds by vasoconstriction. Mild hypothermia may be detected mainly by endothelium, while the temperature below approx. 30 °C may directly affect the smooth muscle. The vascular response to temperatures below 20 °C was endothelium-independent [60]. Various TRP channels are thought to be temperature sensitive. The TRPV₃ and TRPV₄ channels are highly sensitive to temperatures around 30 °C. The TRPM₈ channels opening at temperatures lower than 20 °C are the best understood cold-sensitive TRP channels. The mammalian TRPA₁ may be another cold sensor which opens at temperatures below 10 °C [316]. Different vessels response differently to temperature changes. For example, the canine coronary artery responded to hypothermia endothelium-independently, while the canine renal and femoral arteries endothelium-dependently [60].

Chemical stimuli

Chemical stimuli have either intracellular or plasma membrane targets. The latter are often associated with the GPCR. The resultant effect depends not only on the type of the G protein and the corresponding signaling pathway, but also on the location of the receptor (endothelium vs the smooth muscle). Importantly, the same receptor types can be located on the endothelium, the smooth muscle, or both sites. The activation of the endothelial G_12/13 and the smooth muscle G_q, G_i and G_12/13 receptors gives rise to vasoconstriction. In contrast, the endothelial G_q, G_s and G_i receptors and the G_s receptors of the smooth muscle mediate vasodilatation. This means that particularly for G_q and G_i receptors, it is necessary to distinguish whether they are located on the endothelium, the smooth muscle or both sites. After the activation of the GPCR, the intracellular pathways in the endothelium are analogous to those in the smooth muscle. Last but not least, one substance can act on more receptor types and one receptor type can be linked to more than one intracellular cascade. The complexity of the vasomotor action can be demonstrated using angiotensin II as an example. The vascular effects of angiotensin II are mainly mediated by the AT₁ receptor. Its agonists activate both the G_q/PLC/IP₃ + DAG/PKC and the G_12/13/RhoA/ROCK cascades. In the VSM cells, both cascades promote vasoconstriction. In the endothelium, the G_12/13 pathway is also vasoconstrictive, e.g. the synthesis and release of 20-HETE are thus induced. In contrast, the activation of the endothelial G_q pathway with the activation of eNOS is vasodilatory. Accordingly, the endothelial AT receptors (possibly the AT_1a subtype) are susceptible to the blood-flow induced shear friction, and angiotensin II at low concentrations can trigger the calcium sparks which are important in protection of small resistance arteries against excessive pressure [11, 180]. Other vasoconstrictive substances influence the membrane ion channels directly (e.g. an activator of Ca_v1.2 channels, Bay K8644, or BK_Ca channel blocker, iberiotoxin) or enter the cells and target the components of intracellular signaling pathways, such as cyclases (an inhibitor of soluble guanylate cyclase, ODQ), protein kinases (an activator of PKC, bryostatin 1), ion channels on the SR (an activator of RyR channels, caffeine), or SERCA (an inhibitor, thapsigargin).

Conclusions

The vascular system controls the distribution of blood and the substances dissolved into all body tissues. Together with the heart, the system secures the circulation of blood, which is essential for life. Vasoconstriction and vasodilatation are two important mechanisms to rapidly and efficiently regulate blood flow. Vasoconstriction is sometimes perceived rather negatively because is associated with endothelial dysfunction [223]. This is not quite correct, as vasoconstriction represents an essential part of normal vascular physiology. The adequate vasoconstriction prevents excessive vasodilatation and secures the blood flow and pressure, necessary to supply blood to tissues. This function is guaranteed by several vasoconstrictor signaling pathways that are interconnected in multiple ways. At the same time, they are interconnected with vasodilator mechanisms tightly regulating each other. The close interdependence of the vascular smooth muscle with the vascular endothelium plays prominent role. Perfect orchestration of all components is necessary for vascular homeostasis, guaranteeing quick and efficient responses to immediate need under various circumstances.

Author contribution

J.P. designed and drafted manuscript and approved the final version, P.D. prepared figures and graphical abstract, M.P. made critical comments on chemical aspects, P.M. made critical comments on pharmacological aspects.

Funding

Open access publishing supported by the institutions participating in the CzechELib Transformative Agreement. Authors thank the Czech Research Health Council (project NU21-02–00135) and Charles University (grant GAUK 236923).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval and Consent to participate

Not applicable.

Human ethics

Not applicable.

Consent for publication

All authors have approved the submission.

Clinical trial number

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

1.Adachi T (2010) Modulation of vascular sarco/endoplasmic reticulum calcium ATPase in cardiovascular pathophysiology. Adv Pharmacol 59:165–195. 10.1016/s1054-3589(10)59006-9 [DOI] [PubMed] [Google Scholar]
2.Alarcon-Martinez L, Yemisci M, Dalkara T (2021) Pericyte morphology and function. Histol Histopathol 36:633–643. 10.14670/hh-18-314 [DOI] [PubMed] [Google Scholar]
3.Alp NJ, McAteer MA, Khoo J, Choudhury RP, Channon KM (2004) Increased endothelial tetrahydrobiopterin synthesis by targeted transgenic GTP-cyclohydrolase I overexpression reduces endothelial dysfunction and atherosclerosis in ApoE-knockout mice. Arterioscler Thromb Vasc Biol 24:445–450. 10.1161/01.Atv.0000115637.48689.77 [DOI] [PubMed] [Google Scholar]
4.Álvarez-Santos MD, Álvarez-González M, Estrada-Soto S, Bazán-Perkins B (2020) Regulation of Myosin light-chain phosphatase activity to generate airway smooth muscle hypercontractility. Front Physiol 11:701. 10.3389/fphys.2020.00701 [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Amberg GC, Navedo MF (2013) Calcium dynamics in vascular smooth muscle. Microcirculation 20:281–289. 10.1111/micc.12046 [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Ambudkar IS, de Souza LB, Ong HL (2017) TRPC1, Orai1, and STIM1 in SOCE: Friends in tight spaces. Cell Calcium 63:33–39. 10.1016/j.ceca.2016.12.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
7.Andrea JE, Walsh MP (1992) Protein kinase C of smooth muscle. Hypertension 20:585–595. 10.1161/01.hyp.20.5.585 [DOI] [PubMed] [Google Scholar]
8.Anwar MA, Shalhoub J, Lim CS, Gohel MS, Davies AH (2012) The effect of pressure-induced mechanical stretch on vascular wall differential gene expression. J Vasc Res 49:463–478. 10.1159/000339151 [DOI] [PubMed] [Google Scholar]
9.Anwar MA, Vorkas PA, Li J, Adesina-Georgiadis KN, Reslan OM, Raffetto JD, Want EJ, Khalil RA, Holmes E, Davies AH (2016) Prolonged mechanical circumferential stretch induces metabolic changes in rat inferior vena cava. Eur J Vasc Endovasc Surg 52:544–552. 10.1016/j.ejvs.2016.07.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
10.Araki S, Ito M, Kureishi Y, Feng J, Machida H, Isaka N, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T (2001) Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase. Pflugers Arch 441:596–603. 10.1007/s004240000462 [DOI] [PubMed] [Google Scholar]
11.Arnaudeau S, Macrez-Leprêtre N, Mironneau J (1996) Activation of calcium sparks by angiotensin II in vascular myocytes. Biochem Biophys Res Commun 222:809–815. 10.1006/bbrc.1996.0808 [DOI] [PubMed] [Google Scholar]
12.Asunción-Alvarez D, Palacios J, Ybañez-Julca RO, Rodriguez-Silva CN, Nwokocha C, Cifuentes F, Greensmith DJ (2024) Calcium signaling in endothelial and vascular smooth muscle cells: sex differences and the influence of estrogens and androgens. Am J Physiol Heart Circ Physiol 326:H950-h970. 10.1152/ajpheart.00600.2023 [DOI] [PubMed] [Google Scholar]
13.Augustin HG, Koh GY (2024) A systems view of the vascular endothelium in health and disease. Cell 187:4833–4858. 10.1016/j.cell.2024.07.012 [DOI] [PubMed] [Google Scholar]
14.Austin C, Wray S (2000) Interactions between Ca(2+) and H(+) and functional consequences in vascular smooth muscle. Circ Res 86:355–363. 10.1161/01.res.86.3.355 [DOI] [PubMed] [Google Scholar]
15.Aviv A (1994) Cytosolic Ca2+, Na+/H+ antiport, protein kinase C trio in essential hypertension. Am J Hypertens 7:205–212. 10.1093/ajh/7.2.205 [DOI] [PubMed] [Google Scholar]
16.Balafanova Z, Bolli R, Zhang J, Zheng Y, Pass J, Bhatnagar A, Tang X-L, Wang O, Cardwell E, Ping P (2002) Nitric Oxide (NO) induces nitration of protein kinase Cε (PKCε), facilitating PKCε translocation via enhanced PKCε-RACK2 interactions. J Biol Chem 277:15021–15027 [DOI] [PubMed] [Google Scholar]
17.Beech DJ (2012) Orai1 calcium channels in the vasculature. Pflügers Arch Eur J Physiol 463:635–647. 10.1007/s00424-012-1090-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Belin de Chantemele EJ, Stepp DW (2012) Influence of obesity and metabolic dysfunction on the endothelial control in the coronary circulation. J Mol Cell Cardiol 52:840–847. 10.1016/j.yjmcc.2011.08.018 [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Bergdahl A, Gomez MF, Wihlborg AK, Erlinge D, Eyjolfson A, Xu SZ, Beech DJ, Dreja K, Hellstrand P (2005) Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry. Am J Physiol Cell Physiol 288:C872-880. 10.1152/ajpcell.00334.2004 [DOI] [PubMed] [Google Scholar]
20.Berlansky S, Humer C, Sallinger M, Frischauf I (2021) More than just simple interaction between STIM and Orai Proteins: CRAC channel function enabled by a network of interactions with regulatory proteins. Int J Mol Sci 22:471 [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Berra-Romani R, Mazzocco-Spezzia A, Pulina MV, Golovina VA (2008) Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture. Am J Physiol Cell Physiol 295:C779–C790. 10.1152/ajpcell.00173.2008 [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Bertorello AM, Aperia A, Walaas SI, Nairn AC, Greengard P (1991) Phosphorylation of the catalytic subunit of Na+, K(+)-ATPase inhibits the activity of the enzyme. Proc Natl Acad Sci U S A 88:11359–11362. 10.1073/pnas.88.24.11359 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Bhullar SK, Shah AK, Dhalla NS (2019) Store-operated calcium channels: Potential target for the therapy of hypertension. Rev Cardiovasc Med 20:139–151. 10.31083/j.rcm.2019.03.522 [DOI] [PubMed] [Google Scholar]
24.Blatter LA (2017) Tissue specificity: SOCE: Implications for Ca(2+) handling in endothelial cells. Adv Exp Med Biol 993:343–361. 10.1007/978-3-319-57732-6_18 [DOI] [PubMed] [Google Scholar]
25.Boedtkjer E, Praetorius J, Matchkov VV, Stankevicius E, Mogensen S, Füchtbauer AC, Simonsen U, Füchtbauer EM, Aalkjaer C (2011) Disruption of Na+, HCO₃⁻ cotransporter NBCn1 (slc4a7) inhibits NO-mediated vasorelaxation, smooth muscle Ca2⁺ sensitivity, and hypertension development in mice. Circulation 124:1819–1829. 10.1161/circulationaha.110.015974 [DOI] [PubMed] [Google Scholar]
26.Bond M, Kitazawa T, Somlyo AP, Somlyo AV (1984) Release and recycling of calcium by the sarcoplasmic reticulum in guinea-pig portal vein smooth muscle. J Physiol 355:677–695. 10.1113/jphysiol.1984.sp015445 [DOI] [PMC free article] [PubMed] [Google Scholar]
27.Bourmeyster N, Vignais PV (1996) Phosphorylation of Rho GDI stabilizes the Rho A-Rho GDI complex in neutrophil cytosol. Biochem Biophys Res Commun 218:54–60. 10.1006/bbrc.1996.0011 [DOI] [PubMed] [Google Scholar]
28.Brayden JE, Earley S, Nelson MT, Reading S (2008) Transient receptor potential (TRP) channels, vascular tone and autoregulation of cerebral blood flow. Clin Exp Pharmacol Physiol 35:1116–1120. 10.1111/j.1440-1681.2007.04855.x [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Brescia P, Rescigno M (2021) The gut vascular barrier: a new player in the gut–liver–brain axis. Trends Mol Med 27:844–855. 10.1016/j.molmed.2021.06.007 [DOI] [PubMed] [Google Scholar]
30.Brueggemann LI, Mackie AR, Cribbs LL, Freda J, Tripathi A, Majetschak M, Byron KL (2014) Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of vascular Kv7 channels. J Biol Chem 289:2099–2111. 10.1074/jbc.M113.527820 [DOI] [PMC free article] [PubMed] [Google Scholar]
31.Callaghan B, Koh SD, Keef KD (2004) Muscarinic M2 receptor stimulation of Cav1.2b requires phosphatidylinositol 3-kinase, protein kinase C, and c-Src. Circ Res 94:626–633. 10.1161/01.Res.0000118248.17466.B7 [DOI] [PubMed] [Google Scholar]
32.Campinho P, Vilfan A, Vermot J (2020) Blood flow forces in shaping the vascular system: A focus on endothelial cell behavior. Front Physiol 11:552. 10.3389/fphys.2020.00552 [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Cario-Toumaniantz C, Ferland-McCollough D, Chadeuf G, Toumaniantz G, Rodriguez M, Galizzi JP, Lockhart B, Bril A, Scalbert E, Loirand G, Pacaud P (2012) RhoA guanine exchange factor expression profile in arteries: evidence for a Rho kinase-dependent negative feedback in angiotensin II-dependent hypertension. Am J Physiol Cell Physiol 302:C1394-1404. 10.1152/ajpcell.00423.2011 [DOI] [PubMed] [Google Scholar]
34.Carroll MA, Garcia MP, Falck JR, McGiff JC (1992) Cyclooxygenase dependency of the renovascular actions of cytochrome P450-derived arachidonate metabolites. J Pharmacol Exp Ther 260:104–109 [PubMed] [Google Scholar]
35.Cartwright EJ, Oceandy D, Austin C, Neyses L (2011) Ca2+ signalling in cardiovascular disease: the role of the plasma membrane calcium pumps. Sci China Life Sci 54:691–698. 10.1007/s11427-011-4199-1 [DOI] [PubMed] [Google Scholar]
36.Castillo-Galán S, Arenas GA, Iturriaga R (2022) Contribution of STIM-activated TRPC-ORAI channels in pulmonary hypertension induced by chronic sustained and intermittent hypoxia. Curr Vasc Pharmacol 20:272–283. 10.2174/1570161120666220321141805 [DOI] [PubMed] [Google Scholar]
37.Ciavarella C, Motta I, Capri M, Gargiulo M, Pasquinelli G (2024) Heterogeneity and differentiation of the human arterial tree: Focus on microRNA expression in vascular disease. Biomolecules 14. 10.3390/biom14030343 [DOI] [PMC free article] [PubMed]
38.Cioffi DL (2011) Redox regulation of endothelial canonical transient receptor potential channels. Antioxid Redox Signal 15:1567–1582. 10.1089/ars.2010.3740 [DOI] [PMC free article] [PubMed] [Google Scholar]
39.Cioffi DL, Wu S, Chen H, Alexeyev M, St. Croix CM, Pitt BR, Uhlig S, Stevens T (2012) Orai1 determines calcium selectivity of an endogenous TRPC heterotetramer channel. Circulation Res 110:1435–1444. 10.1161/CIRCRESAHA.112.269506 [DOI] [PMC free article] [PubMed] [Google Scholar]
40.Cipolla MJ, Curry AB (2002) Middle cerebral artery function after stroke: the threshold duration of reperfusion for myogenic activity. Stroke 33:2094–2099. 10.1161/01.str.0000020712.84444.8d [DOI] [PubMed] [Google Scholar]
41.Clapham DE (2007) Calcium signaling. Cell 131:1047–1058. 10.1016/j.cell.2007.11.028 [DOI] [PubMed] [Google Scholar]
42.Collier ML, Ji G, Wang Y, Kotlikoff MI (2000) Calcium-induced calcium release in smooth muscle: loose coupling between the action potential and calcium release. J Gen Physiol 115:653–662. 10.1085/jgp.115.5.653 [DOI] [PMC free article] [PubMed] [Google Scholar]
43.Colyer J (1998) Phosphorylation states of phospholamban. Ann N Y Acad Sci 853:79–91. 10.1111/j.1749-6632.1998.tb08258.x [DOI] [PubMed] [Google Scholar]
44.Cox RH, Petrou S (1999) Ca(2+) influx inhibits voltage-dependent and augments Ca(2+)-dependent K(+) currents in arterial myocytes. Am J Physiol 277:C51-63. 10.1152/ajpcell.1999.277.1.C51 [DOI] [PubMed] [Google Scholar]
45.Cui Y, Gollasch M, Kassmann M (2023) Arterial myogenic response and aging. Ageing Res Rev 84:101813. 10.1016/j.arr.2022.101813 [DOI] [PubMed] [Google Scholar]
46.Cui Y, Kassmann M, Nickel S, Zhang C, Alenina N, Anistan YM, Schleifenbaum J, Bader M, Welsh DG, Huang Y, Gollasch M (2022) Myogenic vasoconstriction requires canonical G(q/11) signaling of the Angiotensin II type 1 receptor. J Am Heart Assoc 11:e022070. 10.1161/jaha.121.022070 [DOI] [PMC free article] [PubMed] [Google Scholar]
47.Cui Z, Zhang Y, Sheng L (2024) Targeting STIM1 contributes to alleviating remodeling of vascular smooth muscle cells in atherosclerosis. Discov Med 36:1678–1691. 10.24976/Discov.Med.202436187.154 [DOI] [PubMed] [Google Scholar]
48.Dedkova EN, Blatter LA (2002) Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum Ca2+ uptake in bovine vascular endothelial cells. J Physiol 539:77–91. 10.1113/jphysiol.2001.013258 [DOI] [PMC free article] [PubMed] [Google Scholar]
49.Dee RA, Mangum KD, Bai X, Mack CP, Taylor JM (2019) Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure. Pharmacol Ther 193:121–134. 10.1016/j.pharmthera.2018.09.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
50.Deissler HL, Lang GE (2016) The protein kinase C inhibitor: Ruboxistaurin. Dev Ophthalmol 55:295–301. 10.1159/000431204 [DOI] [PubMed] [Google Scholar]
51.Dubois T, Oudinet JP, Mira JP, Russo-Marie F (1996) Annexins and protein kinases C. Biochim Biophys Acta 1313:290–294. 10.1016/0167-4889(96)00102-4 [DOI] [PubMed] [Google Scholar]
52.Dulhunty AF, Pouliquin P (2003) What we don’t know about the structure of ryanodine receptor calcium release channels. Clin Exp Pharmacol Physiol 30:713–723. 10.1046/j.1440-1681.2003.03904.x [DOI] [PubMed] [Google Scholar]
53.Dunaway LS, Mills WA 3rd, Eyo UB, Isakson BE (2025) The Cells of the vasculature: advances in the regulation of vascular tone in the brain and periphery. Basic Clin Pharmacol Toxicol 136:e70023. 10.1111/bcpt.70023 [DOI] [PMC free article] [PubMed] [Google Scholar]
54.Dupuis J, Hoeper MM (2008) Endothelin receptor antagonists in pulmonary arterial hypertension. Eur Respir J 31:407–415. 10.1183/09031936.00078207 [DOI] [PubMed] [Google Scholar]
55.Earley S, Brayden JE (2015) Transient receptor potential channels in the vasculature. Physiol Rev 95:645–690. 10.1152/physrev.00026.2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
56.Eid AH (2025) A Game changer for resistant hypertension: The rise of aprocitentan. J Cardiovasc Pharmacol 85:312–315. 10.1097/fjc.0000000000001679 [DOI] [PubMed] [Google Scholar]
57.El Assar M, García-Rojo E, Sevilleja-Ortiz A, Sánchez-Ferrer A, Fernández A, García-Gómez B, Romero-Otero J, Rodríguez-Mañas L, Angulo J (2022) Functional role of STIM-1 and Orai1 in human microvascular aging. Cells 11. 10.3390/cells11223675 [DOI] [PMC free article] [PubMed]
58.Emrich SM, Yoast RE, Xin P, Arige V, Wagner LE, Hempel N, Gill DL, Sneyd J, Yule DI, Trebak M (2021) Omnitemporal choreographies of all five STIM/Orai and IP(3)Rs underlie the complexity of mammalian Ca(2+) signaling. Cell Rep 34:108760. 10.1016/j.celrep.2021.108760 [DOI] [PMC free article] [PubMed] [Google Scholar]
59.Evans AM (2017) Nanojunctions of the sarcoplasmic reticulum deliver site- and function-specific calcium signaling in vascular smooth muscles. Adv Pharmacol 78:1–47. 10.1016/bs.apha.2016.10.001 [DOI] [PubMed] [Google Scholar]
60.Evora PR, Cable DG, Chua YL, Rodrigues AJ, Pearson PJ, Schaff HV (2007) Nitric oxide and prostacyclin-dependent pathways involvement on in vitro induced hypothermia. Cryobiology 54:106–113. 10.1016/j.cryobiol.2006.12.002 [DOI] [PubMed] [Google Scholar]
61.Fan G, Cui Y, Gollasch M, Kassmann M (2019) Elementary calcium signaling in arterial smooth muscle. Channels (Austin) 13:505–519. 10.1080/19336950.2019.1688910 [DOI] [PMC free article] [PubMed] [Google Scholar]
62.Fang X, Faraci FM, Kaduce TL, Harmon S, Modrick ML, Hu S, Moore SA, Falck JR, Weintraub NL, Spector AA (2006) 20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: role of cyclooxygenase. Am J Physiol Heart Circ Physiol 291:H2301-2307. 10.1152/ajpheart.00349.2006 [DOI] [PubMed] [Google Scholar]
63.Fantozzi I, Zhang S, Platoshyn O, Remillard CV, Cowling RT, Yuan JX (2003) Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 285:L1233-1245. 10.1152/ajplung.00445.2002 [DOI] [PubMed] [Google Scholar]
64.Félétou M, Verbeuren TJ, Vanhoutte PM (2009) Endothelium-dependent contractions in SHR: a tale of prostanoid TP and IP receptors. Br J Pharmacol 156:563–574. 10.1111/j.1476-5381.2008.00060.x [DOI] [PMC free article] [PubMed] [Google Scholar]
65.Fill M, Copello JA (2002) Ryanodine receptor calcium release channels. Physiol Rev 82:893–922. 10.1152/physrev.00013.2002 [DOI] [PubMed] [Google Scholar]
66.Finkel T, Menazza S, Holmström KM, Parks RJ, Liu J, Sun J, Liu J, Pan X, Murphy E (2015) The ins and outs of mitochondrial calcium. Circ Res 116:1810–1819. 10.1161/circresaha.116.305484 [DOI] [PMC free article] [PubMed] [Google Scholar]
67.Fleissner F, Thum T (2011) Critical role of the nitric oxide/reactive oxygen species balance in endothelial progenitor dysfunction. Antioxid Redox Signal 15:933–948. 10.1089/ars.2010.3502 [DOI] [PMC free article] [PubMed] [Google Scholar]
68.Foote CA, Soares RN, Ramirez-Perez FI, Ghiarone T, Aroor A, Manrique-Acevedo C, Padilla J, Martinez-Lemus L (2022) Endothelial Glycocalyx. Compr Physiol 12:3781–3811. 10.1002/cphy.c210029 [DOI] [PMC free article] [PubMed] [Google Scholar]
69.Foskett JK, White C, Cheung KH, Mak DO (2007) Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev 87:593–658. 10.1152/physrev.00035.2006 [DOI] [PMC free article] [PubMed] [Google Scholar]
70.Fuloria M, Eckman DM, Leach DA, Aschner JL (2004) 20-hydroxyeicosatetraenoic acid is a vasoconstrictor in the newborn piglet pulmonary microcirculation. Am J Physiol Lung Cell Mol Physiol 287:L360-365. 10.1152/ajplung.00358.2003 [DOI] [PubMed] [Google Scholar]
71.Gao Y, Chen Z, Leung SW, Vanhoutte PM (2015) Hypoxic vasospasm mediated by cIMP: When soluble guanylyl cyclase turns bad. J Cardiovasc Pharmacol 65:545–548. 10.1097/fjc.0000000000000167 [DOI] [PMC free article] [PubMed] [Google Scholar]
72.Ghosh D, Syed AU, Prada MP, Nystoriak MA, Santana LF, Nieves-Cintrón M, Navedo MF (2017) Calcium channels in vascular smooth muscle. Adv Pharmacol 78:49–87. 10.1016/bs.apha.2016.08.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
73.Giachini FR, Chiao CW, Carneiro FS, Lima VV, Carneiro ZN, Dorrance AM, Tostes RC, Webb RC (2009) Increased activation of stromal interaction molecule-1/Orai-1 in aorta from hypertensive rats: a novel insight into vascular dysfunction. Hypertension 53:409–416. 10.1161/hypertensionaha.108.124404 [DOI] [PMC free article] [PubMed] [Google Scholar]
74.Giachini FR, Webb RC, Tostes RC (2009) STIM and Orai proteins: players in sexual differences in hypertension-associated vascular dysfunction? Clin Sci (Lond) 118:391–396. 10.1042/cs20090449 [DOI] [PMC free article] [PubMed] [Google Scholar]
75.Gilbert-Honick J, Grayson W (2020) Vascularized and innervated skeletal muscle tissue engineering. Adv Healthc Mater 9:e1900626. 10.1002/adhm.201900626 [DOI] [PMC free article] [PubMed] [Google Scholar]
76.Glavind-Kristensen M, Matchkov V, Hansen VB, Forman A, Nilsson H, Aalkjaer C (2004) KATP-channel-induced vasodilation is modulated by the Na,K-pump activity in rabbit coronary small arteries. Br J Pharmacol 143:872–880. 10.1038/sj.bjp.0706016 [DOI] [PMC free article] [PubMed] [Google Scholar]
77.Gluais P, Lonchampt M, Morrow JD, Vanhoutte PM, Feletou M (2005) Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin. Br J Pharmacol 146:834–845. 10.1038/sj.bjp.0706390 [DOI] [PMC free article] [PubMed] [Google Scholar]
78.Gluais P, Paysant J, Badier-Commander C, Verbeuren T, Vanhoutte PM, Félétou M (2006) In SHR aorta, calcium ionophore A-23187 releases prostacyclin and thromboxane A2 as endothelium-derived contracting factors. Am J Physiol Heart Circ Physiol 291:H2255-2264. 10.1152/ajpheart.01115.2005 [DOI] [PubMed] [Google Scholar]
79.Goddard J, Webb DJ (2000) Plasma endothelin concentrations in hypertension. J Cardiovasc Pharmacol 35:S25-31. 10.1097/00005344-200000002-00007 [DOI] [PubMed] [Google Scholar]
80.Gollasch M (2012) Vasodilator signals from perivascular adipose tissue. Br J Pharmacol 165:633–642. 10.1111/j.1476-5381.2011.01430.x [DOI] [PMC free article] [PubMed] [Google Scholar]
81.Gollasch M (2017) Adipose-vascular coupling and potential therapeutics. Annu Rev Pharmacol Toxicol 57:417–436. 10.1146/annurev-pharmtox-010716-104542 [DOI] [PubMed] [Google Scholar]
82.Gong MC, Fuglsang A, Alessi D, Kobayashi S, Cohen P, Somlyo AV, Somlyo AP (1992) Arachidonic acid inhibits myosin light chain phosphatase and sensitizes smooth muscle to calcium. J Biol Chem 267:21492–21498 [PubMed] [Google Scholar]
83.Gong MC, Fujihara H, Somlyo AV, Somlyo AP (1997) Translocation of rhoA associated with Ca2+ sensitization of smooth muscle. J Biol Chem 272:10704–10709. 10.1074/jbc.272.16.10704 [DOI] [PubMed] [Google Scholar]
84.Gopalakrishna R, Anderson WB (1989) Ca2+- and phospholipid-independent activation of protein kinase C by selective oxidative modification of the regulatory domain. Proc Natl Acad Sci U S A 86:6758–6762. 10.1073/pnas.86.17.6758 [DOI] [PMC free article] [PubMed] [Google Scholar]
85.Grange JJ, Baca-Regen LM, Nollendorfs AJ, Persidsky Y, Sudan DL, Baxter BT (1998) Protein kinase C isoforms in human aortic smooth muscle cells. J Vasc Surg 27:919–926. 10.1016/s0741-5214(98)70273-3. discussion 926-917 [DOI] [PubMed] [Google Scholar]
86.Griendling KK, Rittenhouse SE, Brock TA, Ekstein LS, Gimbrone MA Jr, Alexander RW (1986) Sustained diacylglycerol formation from inositol phospholipids in angiotensin II-stimulated vascular smooth muscle cells. J Biol Chem 261:5901–5906 [PubMed] [Google Scholar]
87.Grubb S, Lauritzen M, Aalkjær C (2021) Brain capillary pericytes and neurovascular coupling. Comp Biochem Physiol A: Mol Integr Physiol 254:110893. 10.1016/j.cbpa.2020.110893 [DOI] [PubMed] [Google Scholar]
88.Grunz E, Jones B, Lateef O, Sen S, Wilkenson K, Joshi T, Boerman EM (2023) Adventitial macrophage accumulation impairs perivascular nerve function in mesenteric arteries with inflammatory bowel disease. bioRxiv. 10.1101/2023.04.04.535591 [DOI] [PMC free article] [PubMed]
89.Guerrero-Hernández A, Gómez-Viquez L, Guerrero-Serna G, Rueda A (2002) Ryanodine receptors in smooth muscle. Front Biosci 7:d1676-1688. 10.2741/a871 [DOI] [PubMed] [Google Scholar]
90.Halvorson BD, Ahmed M, Huang SJ, Frisbee JC (2024) Scoping review: integration of the major mechanisms underlying the regulation of arteriolar tone. J Vasc Res 61:1–15. 10.1159/000535404 [DOI] [PubMed] [Google Scholar]
91.Hamilton SL, Serysheva II (2009) Ryanodine receptor structure: progress and challenges. J Biol Chem 284:4047–4051. 10.1074/jbc.R800054200 [DOI] [PMC free article] [PubMed] [Google Scholar]
92.Harraz OF, Jensen LJ (2021) Vascular calcium signalling and ageing. J Physiol 599:5361–5377. 10.1113/jp280950 [DOI] [PMC free article] [PubMed] [Google Scholar]
93.Hartmann J, Dragicevic E, Adelsberger H, Henning HA, Sumser M, Abramowitz J, Blum R, Dietrich A, Freichel M, Flockerzi V, Birnbaumer L, Konnerth A (2008) TRPC3 channels are required for synaptic transmission and motor coordination. Neuron 59:392–398. 10.1016/j.neuron.2008.06.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
94.Hartmann S, Ridley A, Lutz S (2015) The function of rho-associated kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease. Front Pharmacol 6. 10.3389/fphar.2015.00276 [DOI] [PMC free article] [PubMed]
95.Hashad AM, Harraz OF, Brett SE, Romero M, Kassmann M, Puglisi JL, Wilson SM, Gollasch M, Welsh DG (2018) Caveolae link Ca(V)3.2 channels to BK(Ca)-Mediated feedback in vascular smooth muscle. Arterioscler Thromb Vasc Biol 38:2371–2381. 10.1161/atvbaha.118.311394 [DOI] [PubMed] [Google Scholar]
96.Heiss EH, Dirsch VM (2014) Regulation of eNOS enzyme activity by posttranslational modification. Curr Pharm Des 20:3503–3513. 10.2174/13816128113196660745 [DOI] [PMC free article] [PubMed] [Google Scholar]
97.Hiley E, McMullan R, Nurrish SJ (2006) The Galpha12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in C. elegans. Embo j 25:5884–5895. 10.1038/sj.emboj.7601458 [DOI] [PMC free article] [PubMed] [Google Scholar]
98.Hill-Eubanks DC, Werner ME, Heppner TJ, Nelson MT (2011) Calcium signaling in smooth muscle. Cold Spring Harb Perspect Biol 3:a004549. 10.1101/cshperspect.a004549 [DOI] [PMC free article] [PubMed] [Google Scholar]
99.Hill BJ, Muldrew E (2014) Oestrogen upregulates the sarcoplasmic reticulum Ca(2+) ATPase pump in coronary arteries. Clin Exp Pharmacol Physiol 41:430–436. 10.1111/1440-1681.12233 [DOI] [PMC free article] [PubMed] [Google Scholar]
100.Hill BJF, Dalton RJ, Joseph BK, Thakali KM, Rusch NJ (2017) 17β-estradiol reduces Ca(v) 1.2 channel abundance and attenuates Ca(2+) -dependent contractions in coronary arteries. Pharmacol Res Perspect 5. 10.1002/prp2.358 [DOI] [PMC free article] [PubMed]
101.Hill MA, Meininger GA (2016) Small artery mechanobiology: Roles of cellular and non-cellular elements. Microcirculation 23:611–613. 10.1111/micc.12323 [DOI] [PubMed] [Google Scholar]
102.Hoefer IE, den Adel B, Daemen MJ (2013) Biomechanical factors as triggers of vascular growth. Cardiovasc Res 99:276–283. 10.1093/cvr/cvt089 [DOI] [PubMed] [Google Scholar]
103.Hofmann T, Chubanov V, Gudermann T, Montell C (2003) TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel. Curr Biol 13:1153–1158. 10.1016/s0960-9822(03)00431-7 [DOI] [PubMed] [Google Scholar]
104.Hoopes SL, Garcia V, Edin ML, Schwartzman ML, Zeldin DC (2015) Vascular actions of 20-HETE. Prostaglandins Other Lipid Mediat 120:9–16. 10.1016/j.prostaglandins.2015.03.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
105.Hou X, Roberts LJ 2nd, Gobeil F Jr, Taber D, Kanai K, Abran D, Brault S, Checchin D, Sennlaub F, Lachapelle P, Varma D, Chemtob S (2004) Isomer-specific contractile effects of a series of synthetic f2-isoprostanes on retinal and cerebral microvasculature. Free Radic Biol Med 36:163–172. 10.1016/j.freeradbiomed.2003.10.024 [DOI] [PubMed] [Google Scholar]
106.Hübner CA, Schroeder BC, Ehmke H (2015) Regulation of vascular tone and arterial blood pressure: role of chloride transport in vascular smooth muscle. Pflugers Arch 467:605–614. 10.1007/s00424-014-1684-y [DOI] [PubMed] [Google Scholar]
107.Huveneers S, Daemen MJ, Hordijk PL (2015) Between Rho(k) and a hard place: the relation between vessel wall stiffness, endothelial contractility, and cardiovascular disease. Circ Res 116:895–908. 10.1161/circresaha.116.305720 [DOI] [PubMed] [Google Scholar]
108.Chakraborty S, Deb BK, Chorna T, Konieczny V, Taylor CW, Hasan G (2016) Mutant IP3 receptors attenuate store-operated Ca2+ entry by destabilizing STIM-Orai interactions in Drosophila neurons. J Cell Sci 129:3903–3910. 10.1242/jcs.191585 [DOI] [PMC free article] [PubMed] [Google Scholar]
109.Chen Z, Zhang X, Ying L, Dou D, Li Y, Bai Y, Liu J, Liu L, Feng H, Yu X, Leung SW, Vanhoutte PM, Gao Y (2014) cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries. Am J Physiol Heart Circ Physiol 307:H328-336. 10.1152/ajpheart.00132.2014 [DOI] [PubMed] [Google Scholar]
110.Cheng H, Lederer WJ, Cannell MB (1993) Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science 262:740–744. 10.1126/science.8235594 [DOI] [PubMed] [Google Scholar]
111.Choi H, Tostes RC, Webb RC (2011) S-nitrosylation Inhibits protein kinase C-mediated contraction in mouse aorta. J Cardiovasc Pharmacol 57:65–71. 10.1097/FJC.0b013e3181fef9cb [DOI] [PMC free article] [PubMed] [Google Scholar]
112.Inagaki M, Yokokura H, Itoh T, Kanmura Y, Kuriyama H, Hidaka H (1987) Purified rabbit brain protein kinase C relaxes skinned vascular smooth muscle and phosphorylates myosin light chain. Arch Biochem Biophys 254:136–141. 10.1016/0003-9861(87)90089-0 [DOI] [PubMed] [Google Scholar]
113.Inoue R, Jensen LJ, Jian Z, Shi J, Hai L, Lurie AI, Henriksen FH, Salomonsson M, Morita H, Kawarabayashi Y, Mori M, Mori Y, Ito Y (2009) Synergistic activation of vascular TRPC6 channel by receptor and mechanical stimulation via phospholipase C/diacylglycerol and phospholipase A2/omega-hydroxylase/20-HETE pathways. Circ Res 104:1399–1409. 10.1161/circresaha.108.193227 [DOI] [PubMed] [Google Scholar]
114.Isakson BE, Ramos SI, Duling BR (2007) Ca2+ and inositol 1,4,5-trisphosphate-mediated signaling across the myoendothelial junction. Circ Res 100:246–254. 10.1161/01.Res.0000257744.23795.93 [DOI] [PubMed] [Google Scholar]
115.Ito K, Hirooka Y, Kimura Y, Shimokawa H, Takeshita A (2005) Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats. Clin Exp Hypertens 27:269–277 [PubMed] [Google Scholar]
116.Ito K, Hirooka Y, Sakai K, Kishi T, Kaibuchi K, Shimokawa H, Takeshita A (2003) Rho/Rho-kinase pathway in brain stem contributes to blood pressure regulation via sympathetic nervous system: possible involvement in neural mechanisms of hypertension. Circ Res 92:1337–1343. 10.1161/01.Res.0000079941.59846.D4 [DOI] [PubMed] [Google Scholar]
117.Jaggar JH, Porter VA, Lederer WJ, Nelson MT (2000) Calcium sparks in smooth muscle. Am J Physiol Cell Physiol 278:C235-256. 10.1152/ajpcell.2000.278.2.C235 [DOI] [PubMed] [Google Scholar]
118.Jaggar JH, Wellman GC, Heppner TJ, Porter VA, Perez GJ, Gollasch M, Kleppisch T, Rubart M, Stevenson AS, Lederer WJ, Knot HJ, Bonev AD, Nelson MT (1998) Ca2+ channels, ryanodine receptors and Ca(2+)-activated K+ channels: a functional unit for regulating arterial tone. Acta Physiol Scand 164:577–587. 10.1046/j.1365-201X.1998.00462.x [DOI] [PubMed] [Google Scholar]
119.Jankowich M, Choudhary G (2020) Endothelin-1 levels and cardiovascular events. Trends Cardiovasc Med 30:1–8. 10.1016/j.tcm.2019.01.007 [DOI] [PubMed] [Google Scholar]
120.Je HD, Gangopadhyay SS, Ashworth TD, Morgan KG (2001) Calponin is required for agonist-induced signal transduction–evidence from an antisense approach in ferret smooth muscle. J Physiol 537:567–577. 10.1111/j.1469-7793.2001.00567.x [DOI] [PMC free article] [PubMed] [Google Scholar]
121.Jho D, Mehta D, Ahmmed G, Gao X-P, Tiruppathi C, Broman M, Malik AB (2005) Angiopoietin-1 Opposes VEGF-Induced Increase in Endothelial Permeability by Inhibiting TRPC1-Dependent Ca2 Influx. Circ Res 96:1282–1290. 10.1161/01.RES.0000171894.03801.03 [DOI] [PubMed] [Google Scholar]
122.Johnson JA, Barman SA (2004) Protein kinase C modulation of cyclic GMP in rat neonatal pulmonary vascular smooth muscle. Lung 182:79–89. 10.1007/s00408-003-1046-6 [DOI] [PubMed] [Google Scholar]
123.Joyner MJ, Wallin BG, Charkoudian N (2016) Sex differences and blood pressure regulation in humans. Exp Physiol 101:349–355. 10.1113/ep085146 [DOI] [PubMed] [Google Scholar]
124.Jufri NF, Mohamedali A, Avolio A, Baker MS (2015) Mechanical stretch: physiological and pathological implications for human vascular endothelial cells. Vasc Cell 7:8. 10.1186/s13221-015-0033-z [DOI] [PMC free article] [PubMed] [Google Scholar]
125.Kaneko T, Amano M, Maeda A, Goto H, Takahashi K, Ito M, Kaibuchi K (2000) Identification of calponin as a novel substrate of Rho-kinase. Biochem Biophys Res Commun 273:110–116. 10.1006/bbrc.2000.2901 [DOI] [PubMed] [Google Scholar]
126.Katada T, Gilman AG, Watanabe Y, Bauer S, Jakobs KH (1985) Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur J Biochem 151:431–437. 10.1111/j.1432-1033.1985.tb09120.x [DOI] [PubMed] [Google Scholar]
127.Katusic ZS, Shepherd JT, Vanhoutte PM (1987) Endothelium-dependent contraction to stretch in canine basilar arteries. Am J Physiol 252:H671-673. 10.1152/ajpheart.1987.252.3.H671 [DOI] [PubMed] [Google Scholar]
128.Kawasaki H, Takatori S, Zamami Y, Koyama T, Goda M, Hirai K, Tangsucharit P, Jin X, Hobara N, Kitamura Y (2011) Paracrine control of mesenteric perivascular axo-axonal interaction. Acta Physiol (Oxf) 203:3–11. 10.1111/j.1748-1716.2010.02197.x [DOI] [PubMed] [Google Scholar]
129.Khaddaj Mallat R, Mathew John C, Kendrick DJ, Braun AP (2017) The vascular endothelium: A regulator of arterial tone and interface for the immune system. Crit Rev Clin Lab Sci 54:458–470. 10.1080/10408363.2017.1394267 [DOI] [PubMed] [Google Scholar]
130.Kikkawa U, Takai Y, Tanaka Y, Miyake R, Nishizuka Y (1983) Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters. J Biol Chem 258:11442–11445 [PubMed] [Google Scholar]
131.Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG (2008) Smooth muscle signalling pathways in health and disease. J Cell Mol Med 12:2165–2180. 10.1111/j.1582-4934.2008.00552.x [DOI] [PMC free article] [PubMed] [Google Scholar]
132.Kim HR, Gallant C, Morgan KG (2013) Regulation of PKC autophosphorylation by calponin in contractile vascular smooth muscle tissue. Biomed Res Int 2013:358643. 10.1155/2013/358643 [DOI] [PMC free article] [PubMed] [Google Scholar]
133.Kim HR, Gallant C, Morgan KG (2013) Regulation of PKC autophosphorylation by calponin in contractile vascular smooth muscle tissue. Biomed Res Int 2013:358643–358643. 10.1155/2013/358643 [DOI] [PMC free article] [PubMed] [Google Scholar]
134.Kitazawa T, Eto M, Woodsome TP, Brautigan DL (2000) Agonists trigger G protein-mediated activation of the CPI-17 inhibitor phosphoprotein of myosin light chain phosphatase to enhance vascular smooth muscle contractility. J Biol Chem 275:9897–9900. 10.1074/jbc.275.14.9897 [DOI] [PubMed] [Google Scholar]
135.Kitazawa T, Kitazawa K (2012) Size-dependent heterogeneity of contractile Ca2+ sensitization in rat arterial smooth muscle. J Physiol 590:5401–5423. 10.1113/jphysiol.2012.241315 [DOI] [PMC free article] [PubMed] [Google Scholar]
136.Knot HJ, Nelson MT (1998) Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure. J Physiol 508(Pt 1):199–209. 10.1111/j.1469-7793.1998.199br.x [DOI] [PMC free article] [PubMed] [Google Scholar]
137.Kold-Petersen H, Brøndum E, Nilsson H, Flyvbjerg A, Aalkjaer C (2012) Impaired myogenic tone in isolated cerebral and coronary resistance arteries from the goto-kakizaki rat model of type 2 diabetes. J Vasc Res 49:267–278. 10.1159/000335487 [DOI] [PubMed] [Google Scholar]
138.Kolettis TM, Barton M, Langleben D, Matsumura Y (2013) Endothelin in coronary artery disease and myocardial infarction. Cardiol Rev 21:249–256. 10.1097/CRD.0b013e318283f65a [DOI] [PubMed] [Google Scholar]
139.Kozai D, Ogawa N, Mori Y (2014) Redox regulation of transient receptor potential channels. Antioxid Redox Signal 21:971–986. 10.1089/ars.2013.5616 [DOI] [PubMed] [Google Scholar]
140.Kur J, Bankhead P, Scholfield CN, Curtis TM, McGeown JG (2013) Ca(2+) sparks promote myogenic tone in retinal arterioles. Br J Pharmacol 168:1675–1686. 10.1111/bph.12044 [DOI] [PMC free article] [PubMed] [Google Scholar]
141.Lacruz RS, Feske S (2015) Diseases caused by mutations in ORAI1 and STIM1. Ann N Y Acad Sci 1356:45–79. 10.1111/nyas.12938 [DOI] [PMC free article] [PubMed] [Google Scholar]
142.Laffin LJ, Bakris GL (2015) Endothelin antagonism and hypertension: an evolving target. Semin Nephrol 35:168–175. 10.1016/j.semnephrol.2015.03.001 [DOI] [PubMed] [Google Scholar]
143.Lagaud GJ, Skarsgard PL, Laher I, van Breemen C (1999) Heterogeneity of endothelium-dependent vasodilation in pressurized cerebral and small mesenteric resistance arteries of the rat. J Pharmacol Exp Ther 290:832–839 [PubMed] [Google Scholar]
144.Lamping KG, Wess J, Cui Y, Nuno DW, Faraci FM (2004) Muscarinic (M) receptors in coronary circulation: gene-targeted mice define the role of M2 and M3 receptors in response to acetylcholine. Arterioscler Thromb Vasc Biol 24:1253–1258. 10.1161/01.ATV.0000130661.82773.ca [DOI] [PubMed] [Google Scholar]
145.Lanner JT, Georgiou DK, Joshi AD, Hamilton SL (2010) Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol 2:a003996. 10.1101/cshperspect.a003996 [DOI] [PMC free article] [PubMed] [Google Scholar]
146.Lanza GA, Shimokawa H (2023) Management of Coronary Artery Spasm. Eur Cardiol 18:e38. 10.15420/ecr.2022.47 [DOI] [PMC free article] [PubMed] [Google Scholar]
147.Large WA, Wang Q (1996) Characteristics and physiological role of the Ca(2+)-activated Cl- conductance in smooth muscle. Am J Physiol 271:C435-454. 10.1152/ajpcell.1996.271.2.C435 [DOI] [PubMed] [Google Scholar]
148.Laufs U, Liao JK (1998) Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 273:24266–24271. 10.1074/jbc.273.37.24266 [DOI] [PubMed] [Google Scholar]
149.Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP (2002) TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell 109:397–407. 10.1016/s0092-8674(02)00719-5 [DOI] [PubMed] [Google Scholar]
150.Laver DR (2018) Regulation of the RyR channel gating by Ca(2+) and Mg(2). Biophys Rev 10:1087–1095. 10.1007/s12551-018-0433-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
151.LeCouter J, Moritz DR, Li B, Phillips GL, Liang XH, Gerber HP, Hillan KJ, Ferrara N (2003) Angiogenesis-independent endothelial protection of liver: role of VEGFR-1. Science 299:890–893. 10.1126/science.1079562 [DOI] [PubMed] [Google Scholar]
152.Ledoux J, Gee DM, Leblanc N (2003) Increased peripheral resistance in heart failure: new evidence suggests an alteration in vascular smooth muscle function. Br J Pharmacol 139:1245–1248. 10.1038/sj.bjp.0705366 [DOI] [PMC free article] [PubMed] [Google Scholar]
153.Ledoux J, Werner ME, Brayden JE, Nelson MT (2006) Calcium-activated potassium channels and the regulation of vascular tone. Physiology (Bethesda) 21:69–78. 10.1152/physiol.00040.2005 [DOI] [PubMed] [Google Scholar]
154.Li T, Thoen ZE, Applebaum JM, Khalil RA (2025) Menopause-related changes in vascular signaling by sex hormones. J Pharmacol Exp Ther 392:103526. 10.1016/j.jpet.2025.103526 [DOI] [PubMed] [Google Scholar]
155.Li T, Yang GM, Zhu Y, Wu Y, Chen XY, Lan D, Tian KL, Liu LM (2015) Diabetes and hyperlipidemia induce dysfunction of VSMCs: contribution of the metabolic inflammation/miRNA pathway. Am J Physiol Endocrinol Metab 308:E257-269. 10.1152/ajpendo.00348.2014 [DOI] [PubMed] [Google Scholar]
156.Li W, Zhu K, Liu Y, Liu M, Chen Q (2025) Recent advances in PKC inhibitor development: Structural design strategies and therapeutic applications. Eur J Med Chem 287:117290. 10.1016/j.ejmech.2025.117290 [DOI] [PubMed] [Google Scholar]
157.Li X, Zhao G, Ma B, Li R, Hong J, Liu S, Wang DW (2014) 20-Hydroxyeicosatetraenoic acid impairs endothelial insulin signaling by inducing phosphorylation of the insulin receptor substrate-1 at Ser616. PLoS One 9:e95841. 10.1371/journal.pone.0095841 [DOI] [PMC free article] [PubMed] [Google Scholar]
158.Liang CF, Liu JT, Wang Y, Xu A, Vanhoutte PM (2013) Toll-like receptor 4 mutation protects obese mice against endothelial dysfunction by decreasing NADPH oxidase isoforms 1 and 4. Arterioscler Thromb Vasc Biol 33:777–784. 10.1161/atvbaha.112.301087 [DOI] [PubMed] [Google Scholar]
159.Lillestłl IK, Helle KB, Aardal S (1998) Relaxing effects of cyclic GMP and cyclic AMP-enhancing agents on the long-lasting contraction to endothelin-1 in the porcine coronary artery. Scand J Clin Lab Invest 58:625–634. 10.1080/00365519850186058 [DOI] [PubMed] [Google Scholar]
160.Lindsey SH, Liu L, Chappell MC (2014) Vasodilation by GPER in mesenteric arteries involves both endothelial nitric oxide and smooth muscle cAMP signaling. Steroids 81:99–102. 10.1016/j.steroids.2013.10.017 [DOI] [PMC free article] [PubMed] [Google Scholar]
161.Liu X, Luo D, Zhang J, Du L (2020) Distribution and relative expression of vasoactive receptors on arteries. Sci Rep 10:15383. 10.1038/s41598-020-72352-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
162.Liu Z, Khalil RA (2018) Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease. Biochem Pharmacol 153:91–122. 10.1016/j.bcp.2018.02.012 [DOI] [PMC free article] [PubMed] [Google Scholar]
163.Loirand G (2015) Rho kinases in health and disease: From basic science to translational research. Pharmacol Rev 67:1074–1095. 10.1124/pr.115.010595 [DOI] [PubMed] [Google Scholar]
164.Loirand G, Guilluy C, Pacaud P (2006) Regulation of Rho proteins by phosphorylation in the cardiovascular system. Trends Cardiovasc Med 16:199–204. 10.1016/j.tcm.2006.03.010 [DOI] [PubMed] [Google Scholar]
165.Longden TA, Isaacs D (2025) Pericyte electrical signalling and brain haemodynamics. Basic Clin Pharmacol Toxicol 136:e70030. 10.1111/bcpt.70030 [DOI] [PMC free article] [PubMed] [Google Scholar]
166.Lopez JJ, Jardin I, Sanchez-Collado J, Salido GM, Smani T, Rosado JA (2020) TRPC channels in the SOCE Scenario. Cells 9(1). 10.3390/cells9010126 [DOI] [PMC free article] [PubMed]
167.Lu D, Kassab GS (2011) Role of shear stress and stretch in vascular mechanobiology. J R Soc Interface 8:1379–1385. 10.1098/rsif.2011.0177 [DOI] [PMC free article] [PubMed] [Google Scholar]
168.Lu X, Kassab GS (2015) Integrins mediate mechanical compression-induced endothelium-dependent vasodilation through endothelial nitric oxide pathway. J Gen Physiol 146:221–232. 10.1085/jgp.201411350 [DOI] [PMC free article] [PubMed] [Google Scholar]
169.Luykenaar KD, Brett SE, Wu BN, Wiehler WB, Welsh DG (2004) Pyrimidine nucleotides suppress KDR currents and depolarize rat cerebral arteries by activating Rho kinase. Am J Physiol-Heart Circulatory Physiol 286:H1088–H1100. 10.1152/ajpheart.00903.2003 [DOI] [PubMed] [Google Scholar]
170.Ma MM, Gao M, Guo KM, Wang M, Li XY, Zeng XL, Sun L, Lv XF, Du YH, Wang GL, Zhou JG, Guan YY (2017) TMEM16A Contributes to endothelial dysfunction by facilitating Nox2 NADPH oxidase-derived reactive oxygen species generation in hypertension. Hypertension 69:892–901. 10.1161/hypertensionaha.116.08874 [DOI] [PubMed] [Google Scholar]
171.Mao Y, Su J, Lei L, Meng L, Qi Y, Huo Y, Tang C (2014) Adrenomedullin and adrenotensin increase the transcription of regulator of G-protein signaling 2 in vascular smooth muscle cells via the cAMP-dependent and PKC pathways. Mol Med Rep 9:323–327. 10.3892/mmr.2013.1751 [DOI] [PubMed] [Google Scholar]
172.Martín-Aragón Baudel MAS, Shi J, Large WA, Albert AP (2020) Insights into activation mechanisms of store-operated TRPC1 channels in vascular smooth muscle. Cells 9:179 [DOI] [PMC free article] [PubMed] [Google Scholar]
173.Maruhashi T, Higashi Y (2021) An overview of pharmacotherapy for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage. Expert Opin Pharmacother 22:1601–1614. 10.1080/14656566.2021.1912013 [DOI] [PubMed] [Google Scholar]
174.Mather KJ, Mirzamohammadi B, Lteif A, Steinberg HO, Baron AD (2002) Endothelin contributes to basal vascular tone and endothelial dysfunction in human obesity and type 2 diabetes. Diabetes 51:3517–3523. 10.2337/diabetes.51.12.3517 [DOI] [PubMed] [Google Scholar]
175.Matchkov VV, Gustafsson H, Rahman A, Briggs Boedtkjer DM, Gorintin S, Hansen AK, Bouzinova EV, Praetorius HA, Aalkjaer C, Nilsson H (2007) Interaction between Na+/K+-pump and Na+/Ca2+-exchanger modulates intercellular communication. Circ Res 100:1026–1035. 10.1161/01.Res.0000262659.09293.56 [DOI] [PubMed] [Google Scholar]
176.Matchkov VV, Krivoi II (2016) Specialized functional diversity and interactions of the Na. K-ATPase Front Physiol 7:179. 10.3389/fphys.2016.00179 [DOI] [PMC free article] [PubMed] [Google Scholar]
177.Matsubara H, Hogan DE, Morgan EF, Mortlock DP, Einhorn TA, Gerstenfeld LC (2012) Vascular tissues are a primary source of BMP2 expression during bone formation induced by distraction osteogenesis. Bone 51:168–180. 10.1016/j.bone.2012.02.017 [DOI] [PMC free article] [PubMed] [Google Scholar]
178.Matsui T, Maeda M, Doi Y, Yonemura S, Amano M, Kaibuchi K, Tsukita S, Tsukita S (1998) Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association. J Cell Biol 140:647–657. 10.1083/jcb.140.3.647 [DOI] [PMC free article] [PubMed] [Google Scholar]
179.Mbikou P, Fajmut A, Brumen M, Roux E (2011) Contribution of Rho kinase to the early phase of the calcium-contraction coupling in airway smooth muscle. Exp Physiol 96:240–258. 10.1113/expphysiol.2010.054635 [DOI] [PubMed] [Google Scholar]
180.Mederos y Schnitzler M, Storch U, Meibers S, Nurwakagari P, Breit A, Essin K, Gollasch M, Gudermann T (2008) Gq-coupled receptors as mechanosensors mediating myogenic vasoconstriction. Embo J 27:3092–3103. 10.1038/emboj.2008.233 [DOI] [PMC free article] [PubMed] [Google Scholar]
181.Meens MJ, Mattheij NJ, van Loenen PB, Spijkers LJ, Lemkens P, Nelissen J, Compeer MG, Alewijnse AE, De Mey JG (2012) G-protein βγ subunits in vasorelaxing and anti-endothelinergic effects of calcitonin gene-related peptide. Br J Pharmacol 166:297–308. 10.1111/j.1476-5381.2011.01774.x [DOI] [PMC free article] [PubMed] [Google Scholar]
182.Meissner G (2017) The structural basis of ryanodine receptor ion channel function. J Gen Physiol 149:1065–1089. 10.1085/jgp.201711878 [DOI] [PMC free article] [PubMed] [Google Scholar]
183.Mendonça MC, Koles N, Sellitti DF (2012) Protein kinase C-δ (PKC-δ) and PKC-α mediate Ca(2+)-dependent increases in CNP mRNA in human vascular cells. Vascul Pharmacol 57:98–104. 10.1016/j.vph.2012.05.002 [DOI] [PubMed] [Google Scholar]
184.Miao LN, Pan D, Shi J, Du JP, Chen PF, Gao J, Yu Y, Shi DZ, Guo M (2022) Role and mechanism of PKC-δ for cardiovascular disease: Current status and perspective. Front Cardiovasc Med 9:816369. 10.3389/fcvm.2022.816369 [DOI] [PMC free article] [PubMed] [Google Scholar]
185.Miller BA, Zhang W (2011) TRP channels as mediators of oxidative stress. Adv Exp Med Biol 704:531–544. 10.1007/978-94-007-0265-3_29 [DOI] [PubMed] [Google Scholar]
186.Minami K, Fukuzawa K, Nakaya Y (1993) Protein kinase C inhibits the Ca(2+)-activated K+ channel of cultured porcine coronary artery smooth muscle cells. Biochem Biophys Res Commun 190:263–269. 10.1006/bbrc.1993.1040 [DOI] [PubMed] [Google Scholar]
187.Ming XF, Barandier C, Viswambharan H, Kwak BR, Mach F, Mazzolai L, Hayoz D, Ruffieux J, Rusconi S, Montani JP, Yang Z (2004) Thrombin stimulates human endothelial arginase enzymatic activity via RhoA/ROCK pathway: implications for atherosclerotic endothelial dysfunction. Circulation 110:3708–3714. 10.1161/01.Cir.0000142867.26182.32 [DOI] [PubMed] [Google Scholar]
188.Mironova GY, Kowalewska PM, El-Lakany M, Tran CHT, Sancho M, Zechariah A, Jackson WF, Welsh DG (2023) The conducted vasomotor response and the principles of electrical communication in resistance arteries. Physiol Rev 104:33–84. 10.1152/physrev.00035.2022 [DOI] [PMC free article] [PubMed] [Google Scholar]
189.Mitsui R, Hashitani H (2020) Synchrony of spontaneous Ca(2+) activity in microvascular mural cells. J Smooth Muscle Res 56:1–18. 10.1540/jsmr.56.1 [DOI] [PMC free article] [PubMed] [Google Scholar]
190.Moccia F, Brunetti V, Perna A, Guerra G, Soda T, Berra-Romani R (2023) The molecular heterogeneity of store-operated Ca(2+) entry in vascular endothelial cells: The different roles of Orai1 and TRPC1/TRPC4 channels in the transition from Ca(2+)-selective to non-selective cation currents. Int J Mol Sci 24. 10.3390/ijms24043259 [DOI] [PMC free article] [PubMed]
191.Moccia F, Negri S, Faris P, Berra-Romani R (2020) Targeting the endothelial Ca2+ toolkit to rescue endothelial dysfunction in obesity associated-hypertension. Curr Med Chem 27:240–257 [DOI] [PubMed] [Google Scholar]
192.Moreno JJ (2017) Eicosanoid receptors: Targets for the treatment of disrupted intestinal epithelial homeostasis. Eur J Pharmacol 796:7–19. 10.1016/j.ejphar.2016.12.004 [DOI] [PubMed] [Google Scholar]
193.Morrow JD (2006) The isoprostanes - unique products of arachidonate peroxidation: their role as mediators of oxidant stress. Curr Pharm Des 12:895–902. 10.2174/138161206776055985 [DOI] [PubMed] [Google Scholar]
194.Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ 2nd (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A 87:9383–9387. 10.1073/pnas.87.23.9383 [DOI] [PMC free article] [PubMed] [Google Scholar]
195.Mountian II, Baba-Aïssa F, Jonas JC, De Humbert S, Wuytack F, Parys JB (2001) Expression of Ca(2+) transport genes in platelets and endothelial cells in hypertension. Hypertension 37:135–141. 10.1161/01.hyp.37.1.135 [DOI] [PubMed] [Google Scholar]
196.Nagai H, Kuwahira I, Schwenke DO, Tsuchimochi H, Nara A, Ogura S, Sonobe T, Inagaki T, Fujii Y, Yamaguchi R, Wingenfeld L, Umetani K, Shimosawa T, Yoshida K, Uemura K, Pearson JT, Shirai M (2015) Pulmonary macrophages attenuate hypoxic pulmonary vasoconstriction via β3AR/iNOS pathway in rats exposed to chronic intermittent hypoxia. PLoS One 10:e0131923. 10.1371/journal.pone.0131923 [DOI] [PMC free article] [PubMed] [Google Scholar]
197.Nalli AD, Kumar DP, Al-Shboul O, Mahavadi S, Kuemmerle JF, Grider JR, Murthy KS (2014) Regulation of Gβγi-dependent PLC-β3 activity in smooth muscle: inhibitory phosphorylation of PLC-β3 by PKA and PKG and stimulatory phosphorylation of Gαi-GTPase-activating protein RGS2 by PKG. Cell Biochem Biophys 70:867–880. 10.1007/s12013-014-9992-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
198.Narumiya S, Thumkeo D (2018) Rho signaling research: history, current status and future directions. FEBS Lett 592:1763–1776. 10.1002/1873-3468.13087 [DOI] [PMC free article] [PubMed] [Google Scholar]
199.Negri S, Faris P, Moccia F (2021) Reactive oxygen species and endothelial Ca(2+) signaling: Brothers in arms or partners in crime? Int J Mol Sci 22. 10.3390/ijms22189821 [DOI] [PMC free article] [PubMed]
200.Neylon CB, Richards SM, Larsen MA, Agrotis A, Bobik A (1995) Multiple types of ryanodine receptor/Ca2+ release channels are expressed in vascular smooth muscle. Biochem Biophys Res Commun 215:814–821. 10.1006/bbrc.1995.2536 [DOI] [PubMed] [Google Scholar]
201.Novokhatska T, Tishkin S, Dosenko V, Boldyriev A, Ivanova I, Strielkov I, Soloviev A (2013) Correction of vascular hypercontractility in spontaneously hypertensive rats using shRNAs-induced delta protein kinase C gene silencing. Eur J Pharmacol 718:401–407. 10.1016/j.ejphar.2013.08.003 [DOI] [PubMed] [Google Scholar]
202.Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K (2000) Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem 275:3577–3582. 10.1074/jbc.275.5.3577 [DOI] [PubMed] [Google Scholar]
203.Ohta S, Nishihara J, Oka Y, Todo H, Kumon Y, Sakaki S (1995) Possible mechanism to induce protein kinase C-dependent arterial smooth muscle contraction after subarachnoid haemorrhage. Acta Neurochir (Wien) 137:217–225. 10.1007/bf02187196 [DOI] [PubMed] [Google Scholar]
204.Palacios J, Marusic ET, Lopez NC, Gonzalez M, Michea L (2004) Estradiol-induced expression of N(+)-K(+)-ATPase catalytic isoforms in rat arteries: gender differences in activity mediated by nitric oxide donors. Am J Physiol Heart Circ Physiol 286:H1793-1800. 10.1152/ajpheart.00990.2003 [DOI] [PubMed] [Google Scholar]
205.Paneni F, Diaz Cañestro C, Libby P, Lüscher Thomas F, Camici Giovanni G (2017) The aging cardiovascular system. JACC 69:1952–1967. 10.1016/j.jacc.2017.01.064 [DOI] [PubMed] [Google Scholar]
206.Partovian C, Zhuang Z, Moodie K, Lin M, Ouchi N, Sessa WC, Walsh K, Simons M (2005) PKCalpha activates eNOS and increases arterial blood flow in vivo. Circ Res 97:482–487. 10.1161/01.Res.0000179775.04114.45 [DOI] [PubMed] [Google Scholar]
207.Patrignani P (2003) Aspirin insensitive eicosanoid biosynthesis in cardiovascular disease. Thromb Res 110:281–286. 10.1016/s0049-3848(03)00382-7 [DOI] [PubMed] [Google Scholar]
208.Paudyal V, Thapa R, Basnet S, Sharma M, Surani S, Varon J (2025) Updates on pulmonary hypertension. Open Respir Med J 19:e18743064344024. 10.2174/0118743064344024250203101417 [DOI] [PMC free article] [PubMed] [Google Scholar]
209.Perez-Gutierrez L, Li P, Ferrara N (2024) Endothelial cell diversity: the many facets of the crystal. Febs J 291:3287–3302. 10.1111/febs.16660 [DOI] [PubMed] [Google Scholar]
210.Phan TX, Ton HT, Gulyás H, Pórszász R, Tóth A, Russo R, Kay MW, Sahibzada N, Ahern GP (2022) TRPV1 in arteries enables a rapid myogenic tone. J Physiol 600:1651–1666. 10.1113/jp281873 [DOI] [PMC free article] [PubMed] [Google Scholar]
211.Pires PW, Ko EA, Pritchard HAT, Rudokas M, Yamasaki E, Earley S (2017) The angiotensin II receptor type 1b is the primary sensor of intraluminal pressure in cerebral artery smooth muscle cells. J Physiol 595:4735–4753. 10.1113/jp274310 [DOI] [PMC free article] [PubMed] [Google Scholar]
212.Potier M, Gonzalez JC, Motiani RK, Abdullaev IF, Bisaillon JM, Singer HA, Trebak M (2009) Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration. Faseb j 23:2425–2437. 10.1096/fj.09-131128 [DOI] [PMC free article] [PubMed] [Google Scholar]
213.Potier M, Gonzalez JC, Motiani RK, Abdullaev IF, Bisaillon JM, Singer HA, Trebak M (2009) Evidence for STIM1- and Orail-dependent storeoperated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration. FASEB J 23:2425–2437. 10.1096/fj.09-131128 [DOI] [PMC free article] [PubMed] [Google Scholar]
214.Prakriya M, Lewis RS (2015) Store-operated calcium channels. Physiol Rev 95:1383–1436. 10.1152/physrev.00020.2014 [DOI] [PMC free article] [PubMed] [Google Scholar]
215.Pratt PF, Falck JR, Reddy KM, Kurian JB, Campbell WB (1998) 20-HETE relaxes bovine coronary arteries through the release of prostacyclin. Hypertension 31:237–241. 10.1161/01.hyp.31.1.237 [DOI] [PubMed] [Google Scholar]
216.Pronk MCA, van Bezu JSM, van Nieuw Amerongen GP, van Hinsbergh VWM, Hordijk PL (2019) RhoA, RhoB and RhoC differentially regulate endothelial barrier function. Small GTPases 10:466–484. 10.1080/21541248.2017.1339767 [DOI] [PMC free article] [PubMed] [Google Scholar]
217.Qiao J, Huang F, Lum H (2003) PKA inhibits RhoA activation: a protection mechanism against endothelial barrier dysfunction. Am J Physiol Lung Cell Mol Physiol 284:L972-980. 10.1152/ajplung.00429.2002 [DOI] [PubMed] [Google Scholar]
218.Qin X, Gao A, Hou X, Xu X, Chen L, Sun L, Hao Y, Shi Y (2022) Connexins may play a critical role in cigarette smoke-induced pulmonary hypertension. Arch Toxicol 96:1609–1621. 10.1007/s00204-022-03274-6 [DOI] [PubMed] [Google Scholar]
219.Radeva MY, Waschke J (2018) Mind the gap: mechanisms regulating the endothelial barrier. Acta Physiol (Oxf) 222. 10.1111/apha.12860 [DOI] [PubMed]
220.Rakugi H, Tabuchi Y, Nakamaru M, Nagano M, Higashimori K, Mikami H, Ogihara T, Suzuki N (1990) Evidence for endothelin-1 release from resistance vessels of rats in response to hypoxia. Biochem Biophys Res Commun 169:973–977. 10.1016/0006-291x(90)91989-6 [DOI] [PubMed] [Google Scholar]
221.Randriamboavonjy V, Busse R, Fleming I (2003) 20-HETE-induced contraction of small coronary arteries depends on the activation of Rho-kinase. Hypertension 41:801–806. 10.1161/01.Hyp.0000047240.33861.6b [DOI] [PubMed] [Google Scholar]
222.Raturi A, Simmen T (2013) Where the endoplasmic reticulum and the mitochondrion tie the knot: the mitochondria-associated membrane (MAM). Biochim Biophys Acta 1833:213–224. 10.1016/j.bbamcr.2012.04.013 [DOI] [PubMed] [Google Scholar]
223.Ray A, Ch. Maharana K, Meenakshi S, Singh S (2023) Endothelial dysfunction and its relation in different disorders: Recent update. Health Sci Rev 7:100084. 10.1016/j.hsr.2023.100084 [Google Scholar]
224.Renaud JM, Gramolini A, Light P, Comtois A (1996) Modulation of muscle contractility during fatigue and recovery by ATP sensitive potassium channel. Acta Physiol Scand 156:203–212. 10.1046/j.1365-201X.1996.210000.x [DOI] [PubMed] [Google Scholar]
225.Ringvold HC, Khalil RA (2017) Protein kinase C as regulator of vascular smooth muscle function and potential target in vascular disorders. Adv Pharmacol 78:203–301. 10.1016/bs.apha.2016.06.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
226.Rinne A, Banach K, Blatter LA (2009) Regulation of nuclear factor of activated T cells (NFAT) in vascular endothelial cells. J Mol Cell Cardiol 47:400–410. 10.1016/j.yjmcc.2009.06.010 [DOI] [PMC free article] [PubMed] [Google Scholar]
227.Roberts LJ 2nd, Milne GL (2009) Isoprostanes. J Lipid Res 50(Suppl):S219-223. 10.1194/jlr.R800037-JLR200 [DOI] [PMC free article] [PubMed] [Google Scholar]
228.Rodrigo GC, Standen NB (2005) ATP-sensitive potassium channels. Curr Pharm Des 11:1915–1940. 10.2174/1381612054021015 [DOI] [PubMed] [Google Scholar]
229.Roman RJ, Renic M, Dunn KM, Takeuchi K, Hacein-Bey L (2006) Evidence that 20-HETE contributes to the development of acute and delayed cerebral vasospasm. Neurol Res 28:738–749. 10.1179/016164106x152016 [DOI] [PubMed] [Google Scholar]
230.Ron D, Kazanietz MG (1999) New insights into the regulation of protein kinase C and novel phorbol ester receptors. Faseb j 13:1658–1676 [PubMed] [Google Scholar]
231.Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Veliçelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169:435–445. 10.1083/jcb.200502019 [DOI] [PMC free article] [PubMed] [Google Scholar]
232.Roshanravan H, Kim EY, Dryer SE (2016) 20-Hydroxyeicosatetraenoic acid (20-HETE) modulates canonical transient receptor potential-6 (TRPC6) channels in podocytes. Front Physiol 7:351. 10.3389/fphys.2016.00351 [DOI] [PMC free article] [PubMed] [Google Scholar]
233.Rovetti R, Cui X, Garfinkel A, Weiss JN, Qu Z (2010) Spark-induced sparks as a mechanism of intracellular calcium alternans in cardiac myocytes. Circ Res 106:1582–1591. 10.1161/circresaha.109.213975 [DOI] [PMC free article] [PubMed] [Google Scholar]
234.Saida K, Van Breemen C (1984) Cyclic AMP modulation of adrenoreceptor-mediated arterial smooth muscle contraction. J Gen Physiol 84:307–318. 10.1085/jgp.84.2.307 [DOI] [PMC free article] [PubMed] [Google Scholar]
235.Saint-Martin Willer A, Montani D, Capuano V, Antigny F (2024) Orai1/STIMs modulators in pulmonary vascular diseases. Cell Calcium 121:102892. 10.1016/j.ceca.2024.102892 [DOI] [PubMed] [Google Scholar]
236.Salamanca DA, Khalil RA (2005) Protein kinase C isoforms as specific targets for modulation of vascular smooth muscle function in hypertension. Biochem Pharmacol 70:1537–1547. 10.1016/j.bcp.2005.07.017 [DOI] [PMC free article] [PubMed] [Google Scholar]
237.Saleh S, Albert A, Peppiatt-Wildman C, Large W (2007) Angiotensin II activates two cation conductances with distinct TRPC1 and TRPC6 channel properties in rabbit mesenteric artery myocytes. J Physiol 577:479–495. 10.1113/jphysiol.2006.119305 [DOI] [PMC free article] [PubMed] [Google Scholar]
238.Sandoval YH, Atef ME, Levesque LO, Li Y, Anand-Srivastava MB (2014) Endothelin-1 signaling in vascular physiology and pathophysiology. Curr Vasc Pharmacol 12:202–214. 10.2174/1570161112666140226122054 [DOI] [PubMed] [Google Scholar]
239.Santulli G, Nakashima R, Yuan Q, Marks AR (2017) Intracellular calcium release channels: an update. J Physiol 595:3041–3051. 10.1113/jp272781 [DOI] [PMC free article] [PubMed] [Google Scholar]
240.Shan J, Resnick LM, Liu QY, Wu XC, Barbagallo M, Pang PK (1994) Vascular effects of 17 beta-estradiol in male Sprague-Dawley rats. Am J Physiol 266:H967-973. 10.1152/ajpheart.1994.266.3.H967 [DOI] [PubMed] [Google Scholar]
241.Sharif-Naeini R, Folgering JH, Bichet D, Duprat F, Lauritzen I, Arhatte M, Jodar M, Dedman A, Chatelain FC, Schulte U, Retailleau K, Loufrani L, Patel A, Sachs F, Delmas P, Peters DJ, Honoré E (2009) Polycystin-1 and -2 dosage regulates pressure sensing. Cell 139:587–596. 10.1016/j.cell.2009.08.045 [DOI] [PubMed] [Google Scholar]
242.Shi J, Mori E, Mori Y, Mori M, Li J, Ito Y, Inoue R (2004) Multiple regulation by calcium of murine homologues of transient receptor potential proteins TRPC6 and TRPC7 expressed in HEK293 cells. J Physiol 561:415–432. 10.1113/jphysiol.2004.075051 [DOI] [PMC free article] [PubMed] [Google Scholar]
243.Shi W-W, Yang Y, Shi Y, Jiang C (2012) K(ATP) channel action in vascular tone regulation: from genetics to diseases. Sheng Li Xue Bao 64:1–13 [PMC free article] [PubMed] [Google Scholar]
244.Shi Y, Vanhoutte PM (2008) Oxidative stress and COX cause hyper-responsiveness in vascular smooth muscle of the femoral artery from diabetic rats. Br J Pharmacol 154:639–651. 10.1038/bjp.2008.110 [DOI] [PMC free article] [PubMed] [Google Scholar]
245.Shimokawa H, Sunamura S, Satoh K (2016) RhoA/Rho-Kinase in the cardiovascular system. Circ Res 118:352–366. 10.1161/circresaha.115.306532 [DOI] [PubMed] [Google Scholar]
246.Shin WS, Berkowitz DE, Ryoo SW (2012) Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice. Exp Mol Med 44:594–602. 10.3858/emm.2012.44.10.068 [DOI] [PMC free article] [PubMed] [Google Scholar]
247.Schildknecht S, Ullrich V (2009) Peroxynitrite as regulator of vascular prostanoid synthesis. Arch Biochem Biophys 484:183–189. 10.1016/j.abb.2008.10.023 [DOI] [PubMed] [Google Scholar]
248.Schleifenbaum J, Kassmann M, Szijártó IA, Hercule HC, Tano JY, Weinert S, Heidenreich M, Pathan AR, Anistan YM, Alenina N, Rusch NJ, Bader M, Jentsch TJ, Gollasch M (2014) Stretch-activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries. Circ Res 115:263–272. 10.1161/circresaha.115.302882 [DOI] [PubMed] [Google Scholar]
249.Schmidt K, Dubrovska G, Nielsen G, Fesüs G, Uhrenholt TR, Hansen PB, Gudermann T, Dietrich A, Gollasch M, de Wit C, Köhler R (2010) Amplification of EDHF-type vasodilatations in TRPC1-deficient mice. Br J Pharmacol 161:1722–1733. 10.1111/j.1476-5381.2010.00985.x [DOI] [PMC free article] [PubMed] [Google Scholar]
250.Schofield I, Malik R, Izzard A, Austin C, Heagerty A (2002) Vascular structural and functional changes in type 2 diabetes mellitus: evidence for the roles of abnormal myogenic responsiveness and dyslipidemia. Circulation 106:3037–3043. 10.1161/01.cir.0000041432.80615.a5 [DOI] [PubMed] [Google Scholar]
251.Singh SS, Chauhan A, Brockerhoff H, Chauhan VP (1993) Activation of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. Biochem Biophys Res Commun 195:104–112. 10.1006/bbrc.1993.2016 [DOI] [PubMed] [Google Scholar]
252.Slish DF, Welsh DG, Brayden JE (2002) Diacylglycerol and protein kinase C activate cation channels involved in myogenic tone. Am J Physiol Heart Circ Physiol 283:H2196-2201. 10.1152/ajpheart.00605.2002 [DOI] [PubMed] [Google Scholar]
253.Soma S, Kuwashima H, Matsumura C, Kimura T (2009) Involvement of protein kinase C in the regulation of Na+/Ca2+ exchanger in bovine adrenal chromaffin cells. Clin Exp Pharmacol Physiol 36:717–723. 10.1111/j.1440-1681.2009.05140.x [DOI] [PubMed] [Google Scholar]
254.Somlyo AV, Bond M, Somlyo AP, Scarpa A (1985) Inositol trisphosphate-induced calcium release and contraction in vascular smooth muscle. Proc Natl Acad Sci U S A 82:5231–5235. 10.1073/pnas.82.15.5231 [DOI] [PMC free article] [PubMed] [Google Scholar]
255.Song T, Hao Q, Zheng YM, Liu QH, Wang YX (2015) Inositol 1,4,5-trisphosphate activates TRPC3 channels to cause extracellular Ca2+ influx in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 309:L1455-1466. 10.1152/ajplung.00148.2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
256.Song X, Liu Y, Dong L, Wang Y (2018) Stromal-interacting molecule 1 (Stim1)/Orai1 modulates endothelial permeability in ventilator-induced lung injury. Med Sci Monit 24:9413–9423. 10.12659/msm.911268 [DOI] [PMC free article] [PubMed] [Google Scholar]
257.Steinberg SF (2008) Structural basis of protein kinase C isoform function. Physiol Rev 88:1341–1378. 10.1152/physrev.00034.2007 [DOI] [PMC free article] [PubMed] [Google Scholar]
258.Sumi T, Matsumoto K, Nakamura T (2001) Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase. J Biol Chem 276:670–676. 10.1074/jbc.M007074200 [DOI] [PubMed] [Google Scholar]
259.Suzuki Y (2025) Ca2+ microdomains in vascular smooth muscle cells: Roles in vascular tone regulation and hypertension. J Pharmacol Sci 158:59–67. 10.1016/j.jphs.2025.03.008 [DOI] [PubMed] [Google Scholar]
260.Swain SM, Romac JM, Shahid RA, Pandol SJ, Liedtke W, Vigna SR, Liddle RA (2020) TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation. J Clin Invest 130:2527–2541. 10.1172/jci134111 [DOI] [PMC free article] [PubMed] [Google Scholar]
261.Taguchi K, Kaneko K, Kubo T (2000) Protein kinase C modulates Ca2+-activated K+ channels in cultured rat mesenteric artery smooth muscle cells. Biol Pharm Bull 23:1450–1454. 10.1248/bpb.23.1450 [DOI] [PubMed] [Google Scholar]
262.Tang EH, Leung FP, Huang Y, Feletou M, So KF, Man RY, Vanhoutte PM (2007) Calcium and reactive oxygen species increase in endothelial cells in response to releasers of endothelium-derived contracting factor. Br J Pharmacol 151:15–23. 10.1038/sj.bjp.0707190 [DOI] [PMC free article] [PubMed] [Google Scholar]
263.Tano JY, Schleifenbaum J, Gollasch M (2014) Perivascular adipose tissue, potassium channels, and vascular dysfunction. Arterioscler Thromb Vasc Biol 34:1827–1830. 10.1161/atvbaha.114.303032 [DOI] [PubMed] [Google Scholar]
264.Thillaiappan NB, Chakraborty P, Hasan G, Taylor CW (2019) IP(3) receptors and Ca(2+) entry. Biochim Biophys Acta Mol Cell Res 1866:1092–1100. 10.1016/j.bbamcr.2018.11.007 [DOI] [PubMed] [Google Scholar]
265.Thompson J, Khalil RA (2003) Gender differences in the regulation of vascular tone. Clin Exp Pharmacol Physiol 30:1–15. 10.1046/j.1440-1681.2003.03790.x [DOI] [PubMed] [Google Scholar]
266.Thorin E, Clozel M (2010) The cardiovascular physiology and pharmacology of endothelin-1. Adv Pharmacol 60:1–26. 10.1016/b978-0-12-385061-4.00001-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
267.Thorin E, Webb DJ (2010) Endothelium-derived endothelin-1. Pflugers Arch 459:951–958. 10.1007/s00424-009-0763-y [DOI] [PMC free article] [PubMed] [Google Scholar]
268.Tian XY, Wong WT, Leung FP, Zhang Y, Wang YX, Lee HK, Ng CF, Chen ZY, Yao X, Au CL, Lau CW, Vanhoutte PM, Cooke JP, Huang Y (2012) Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin f(2α) impairs endothelial function in renovascular hypertensive rats. Antioxid Redox Signal 16:363–373. 10.1089/ars.2010.3874 [DOI] [PMC free article] [PubMed] [Google Scholar]
269.Topper JN, Cai J, Falb D, Gimbrone MA Jr (1996) Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A 93:10417–10422. 10.1073/pnas.93.19.10417 [DOI] [PMC free article] [PubMed] [Google Scholar]
270.Toussaint F, Charbel C, Allen BG, Ledoux J (2016) Vascular CaMKII: heart and brain in your arteries. Am J Physiol Cell Physiol 311:C462–C478. 10.1152/ajpcell.00341.2015 [DOI] [PMC free article] [PubMed] [Google Scholar]
271.Touyz RM, Alves-Lopes R, Rios FJ, Camargo LL, Anagnostopoulou A, Arner A, Montezano AC (2018) Vascular smooth muscle contraction in hypertension. Cardiovasc Res 114:529–539. 10.1093/cvr/cvy023 [DOI] [PMC free article] [PubMed] [Google Scholar]
272.Tran QK, Firkins R, Giles J, Francis S, Matnishian V, Tran P, VerMeer M, Jasurda J, Burgard MA, Gebert-Oberle B (2016) Estrogen enhances linkage in the vascular endothelial calmodulin network via a feedforward mechanism at the g protein-coupled estrogen receptor 1. J Biol Chem 291:10805–10823. 10.1074/jbc.M115.697334 [DOI] [PMC free article] [PubMed] [Google Scholar]
273.Treiber FA, Kamarck T, Schneiderman N, Sheffield D, Kapuku G, Taylor T (2003) Cardiovascular reactivity and development of preclinical and clinical disease states. Psychosom Med 65:46–62. 10.1097/00006842-200301000-00007 [DOI] [PubMed] [Google Scholar]
274.Tsang SY, Yao X, Wong CM, Chan FL, Chen ZY, Huang Y (2004) Differential regulation of K+ and Ca2+ channel gene expression by chronic treatment with estrogen and tamoxifen in rat aorta. Eur J Pharmacol 483:155–162. 10.1016/j.ejphar.2003.10.031 [DOI] [PubMed] [Google Scholar]
275.Tu H, Wang Z, Bezprozvanny I (2005) Modulation of mammalian inositol 1,4,5-trisphosphate receptor isoforms by calcium: a role of calcium sensor region. Biophys J 88:1056–1069. 10.1529/biophysj.104.049601 [DOI] [PMC free article] [PubMed] [Google Scholar]
276.Tykocki NR, Boerman EM, Jackson WF (2017) Smooth muscle ion channels and regulation of vascular tone in resistance arteries and arterioles. Compr Physiol 7:485–581. 10.1002/cphy.c160011 [DOI] [PMC free article] [PubMed] [Google Scholar]
277.Ullrich ND, Koschak A, MacLeod KT (2007) Oestrogen directly inhibits the cardiovascular L-type Ca2+ channel Cav1.2. Biochem Biophys Res Commun 361:522–527. 10.1016/j.bbrc.2007.07.054 [DOI] [PubMed] [Google Scholar]
278.van Splunder H, Villacampa P, Martínez-Romero A, Graupera M (2024) Pericytes in the disease spotlight. Trends Cell Biol 34:58–71. 10.1016/j.tcb.2023.06.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
279.Vangeel L, Voets T (2019) Transient receptor potential channels and calcium signaling. Cold Spring Harb Perspect Biol 11. 10.1101/cshperspect.a035048 [DOI] [PMC free article] [PubMed]
280.Vanhoutte PM, Feletou M, Taddei S (2005) Endothelium-dependent contractions in hypertension. Br J Pharmacol 144:449–458. 10.1038/sj.bjp.0706042 [DOI] [PMC free article] [PubMed] [Google Scholar]
281.Vanhoutte PM, Shimokawa H, Feletou M, Tang EH (2017) Endothelial dysfunction and vascular disease - a 30th anniversary update. Acta Physiol (Oxf) 219:22–96. 10.1111/apha.12646 [DOI] [PubMed] [Google Scholar]
282.Vanhoutte PM, Tang EH (2008) Endothelium-dependent contractions: when a good guy turns bad! J Physiol 586:5295–5304. 10.1113/jphysiol.2008.161430 [DOI] [PMC free article] [PubMed] [Google Scholar]
283.Várnai P, Hunyady L, Balla T (2009) STIM and Orai: the long-awaited constituents of store-operated calcium entry. Trends Pharmacol Sci 30:118–128. 10.1016/j.tips.2008.11.005 [DOI] [PMC free article] [PubMed] [Google Scholar]
284.Virdis A, Bacca A, Colucci R, Duranti E, Fornai M, Materazzi G, Ippolito C, Bernardini N, Blandizzi C, Bernini G, Taddei S (2013) Endothelial dysfunction in small arteries of essential hypertensive patients: role of cyclooxygenase-2 in oxidative stress generation. Hypertension 62:337–344. 10.1161/hypertensionaha.111.00995 [DOI] [PubMed] [Google Scholar]
285.Walker JW, Somlyo AV, Goldman YE, Somlyo AP, Trentham DR (1987) Kinetics of smooth and skeletal muscle activation by laser pulse photolysis of caged inositol 1,4,5-trisphosphate. Nature 327:249–252. 10.1038/327249a0 [DOI] [PubMed] [Google Scholar]
286.Wang D, Wang C, Wu X, Zheng W, Sandberg K, Ji H, Welch WJ, Wilcox CS (2014) Endothelial dysfunction and enhanced contractility in microvessels from ovariectomized rats: roles of oxidative stress and perivascular adipose tissue. Hypertension 63:1063–1069. 10.1161/hypertensionaha.113.02284 [DOI] [PMC free article] [PubMed] [Google Scholar]
287.Wang R, Sauvé R, de Champlain J (1995) Abnormal regulation of cytosolic free calcium in vascular endothelial cells from spontaneously hypertensive rats. J Hypertens 13:993–1001 [PubMed] [Google Scholar]
288.Wang Y, Zheng XR, Riddick N, Bryden M, Baur W, Zhang X, Surks HK (2009) ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res 104:531–540. 10.1161/circresaha.108.188524 [DOI] [PMC free article] [PubMed] [Google Scholar]
289.Westcott EB, Jackson WF (2011) Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles. Am J Physiol Heart Circ Physiol 300:H1616-1630. 10.1152/ajpheart.00728.2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
290.Wilson C, Lee MD, McCarron JG (2016) Acetylcholine released by endothelial cells facilitates flow-mediated dilatation. J Physiol 594:7267–7307. 10.1113/jp272927 [DOI] [PMC free article] [PubMed] [Google Scholar]
291.Wilson C, Zhang X, Buckley C, Heathcote HR, Lee MD, McCarron JG (2019) Increased vascular contractility in hypertension results from impaired endothelial calcium signaling. Hypertension 74:1200–1214. 10.1161/hypertensionaha.119.13791 [DOI] [PMC free article] [PubMed] [Google Scholar]
292.Wong MS, Delansorne R, Man RY, Vanhoutte PM (2008) Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 295:H289-296. 10.1152/ajpheart.00116.2008 [DOI] [PubMed] [Google Scholar]
293.Wong MS, Vanhoutte PM (2010) COX-mediated endothelium-dependent contractions: from the past to recent discoveries. Acta Pharmacol Sin 31:1095–1102. 10.1038/aps.2010.127 [DOI] [PMC free article] [PubMed] [Google Scholar]
294.Wong SL, Leung FP, Lau CW, Au CL, Yung LM, Yao X, Chen ZY, Vanhoutte PM, Gollasch M, Huang Y (2009) Cyclooxygenase-2-derived prostaglandin F2alpha mediates endothelium-dependent contractions in the aortae of hamsters with increased impact during aging. Circ Res 104:228–235. 10.1161/circresaha.108.179770 [DOI] [PubMed] [Google Scholar]
295.Woodsome TP, Eto M, Everett A, Brautigan DL, Kitazawa T (2001) Expression of CPI-17 and myosin phosphatase correlates with Ca(2+) sensitivity of protein kinase C-induced contraction in rabbit smooth muscle. J Physiol 535:553–564. 10.1111/j.1469-7793.2001.t01-1-00553.x [DOI] [PMC free article] [PubMed] [Google Scholar]
296.Worley PF, Zeng W, Huang GN, Yuan JP, Kim JY, Lee MG, Muallem S (2007) TRPC channels as STIM1-regulated store-operated channels. Cell Calcium 42:205–211. 10.1016/j.ceca.2007.03.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
297.Wray S, Smith RD (2004) Mechanisms of action of pH-induced effects on vascular smooth muscle. Mol Cell Biochem 263:163–172. 10.1023/B:MCBI.0000041858.78005.d2 [DOI] [PubMed] [Google Scholar]
298.Wright NT, Prosser BL, Varney KM, Zimmer DB, Schneider MF, Weber DJ (2008) S100A1 and calmodulin compete for the same binding site on ryanodine receptor. J Biol Chem 283:26676–26683. 10.1074/jbc.M804432200 [DOI] [PMC free article] [PubMed] [Google Scholar]
299.Wu Y, Fu J, Huang Y, Duan R, Zhang W, Wang C, Wang S, Hu X, Zhao H, Wang L, Liu J, Gao G, Yuan P (2023) Biology and function of pericytes in the vascular microcirculation. Animal Model Exp Med 6:337–345. 10.1002/ame2.12334 [DOI] [PMC free article] [PubMed] [Google Scholar]
300.Xu SZ, Boulay G, Flemming R, Beech DJ (2006) E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles. Am J Physiol Heart Circ Physiol 291:H2653-2659. 10.1152/ajpheart.00495.2006 [DOI] [PubMed] [Google Scholar]
301.Yamada M, Lamping KG, Duttaroy A, Zhang W, Cui Y, Bymaster FP, McKinzie DL, Felder CC, Deng CX, Faraci FM, Wess J (2001) Cholinergic dilation of cerebral blood vessels is abolished in M(5) muscarinic acetylcholine receptor knockout mice. Proc Natl Acad Sci U S A 98:14096–14101. 10.1073/pnas.251542998 [DOI] [PMC free article] [PubMed] [Google Scholar]
302.Yamaguchi H, Igarashi M, Hirata A, Sugae N, Tsuchiya H, Jimbu Y, Tominaga M, Kato T (2004) Altered PDGF-BB-induced p38 MAP kinase activation in diabetic vascular smooth muscle cells: roles of protein kinase C-delta. Arterioscler Thromb Vasc Biol 24:2095–2101. 10.1161/01.Atv.0000144009.35400.65 [DOI] [PubMed] [Google Scholar]
303.Yamaguchi Y, Katoh H, Yasui H, Aoki J, Nakamura K, Negishi M (2000) Galpha(12) and galpha(13) inhibit Ca(2+)-dependent exocytosis through Rho/Rho-associated kinase-dependent pathway. J Neurochem 75:708–717. 10.1046/j.1471-4159.2000.0750708.x [DOI] [PubMed] [Google Scholar]
304.Yamamoto H, van Breemen C (1985) Inositol-1,4,5-trisphosphate releases calcium from skinned cultured smooth muscle cells. Biochem Biophys Res Commun 130:270–274. 10.1016/0006-291x(85)90412-7 [DOI] [PubMed] [Google Scholar]
305.Yang D, Félétou M, Levens N, Zhang JN, Vanhoutte PM (2003) A diffusible substance(s) mediates endothelium-dependent contractions in the aorta of SHR. Hypertension 41:143–148. 10.1161/01.hyp.0000047651.45322.16 [DOI] [PubMed] [Google Scholar]
306.Yang Z, Ming XF (2013) Arginase: the emerging therapeutic target for vascular oxidative stress and inflammation. Front Immunol 4:149. 10.3389/fimmu.2013.00149 [DOI] [PMC free article] [PubMed] [Google Scholar]
307.Yao L, Romero MJ, Toque HA, Yang G, Caldwell RB, Caldwell RW (2010) The role of RhoA/Rho kinase pathway in endothelial dysfunction. J Cardiovasc Dis Res 1:165–170. 10.4103/0975-3583.74258 [DOI] [PMC free article] [PubMed] [Google Scholar]
308.Yeh HI, Chang HM, Lu WW, Lee YN, Ko YS, Severs NJ, Tsai CH (2000) Age-related alteration of gap junction distribution and connexin expression in rat aortic endothelium. J Histochem Cytochem 48:1377–1389. 10.1177/002215540004801008 [DOI] [PubMed] [Google Scholar]
309.Yiu SS, Zhao X, Inscho EW, Imig JD (2003) 12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels. J Lipid Res 44:2391–2399. 10.1194/jlr.M300183-JLR200 [DOI] [PubMed] [Google Scholar]
310.Yu M, McAndrew RP, Al-Saghir R, Maier KG, Medhora M, Roman RJ (1985) Jacobs ER (2002) Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries. J Appl Physiol 93:1391–1399. 10.1152/japplphysiol.00247.2002 [DOI] [PubMed] [Google Scholar]
311.Yu X, Ma H, Barman SA, Liu AT, Sellers M, Stallone JN, Prossnitz ER, White RE, Han G (2011) Activation of G protein-coupled estrogen receptor induces endothelium-independent relaxation of coronary artery smooth muscle. Am J Physiol Endocrinol Metab 301:E882-888. 10.1152/ajpendo.00037.2011 [DOI] [PMC free article] [PubMed] [Google Scholar]
312.Zeng Q, Han Y, Bao Y, Li W, Li X, Shen X, Wang X, Yao F, O’Rourke ST, Sun C (2010) 20-HETE increases NADPH oxidase-derived ROS production and stimulates the L-type Ca2+ channel via a PKC-dependent mechanism in cardiomyocytes. Am J Physiol Heart Circ Physiol 299:H1109-1117. 10.1152/ajpheart.00067.2010 [DOI] [PMC free article] [PubMed] [Google Scholar]
313.Zhai H, Liu H, Shang B, Zou X (2023) Sarsasapogenin blocks ox-LDL-stimulated vascular smooth muscle cell proliferation, migration, and invasion through suppressing STIM1 expression. Cardiovasc Diagn Ther 13:441–452. 10.21037/cdt-23-111 [DOI] [PMC free article] [PubMed] [Google Scholar]
314.Zhang F, Ram JL, Standley PR, Sowers JR (1994) 17 beta-Estradiol attenuates voltage-dependent Ca2+ currents in A7r5 vascular smooth muscle cell line. Am J Physiol 266:C975-980. 10.1152/ajpcell.1994.266.4.C975 [DOI] [PubMed] [Google Scholar]
315.Zhao T, Parmisano S, Soroureddin Z, Zhao M, Yung L, Thistlethwaite PA, Makino A, Yuan JX (2022) Mechanosensitive cation currents through TRPC6 and Piezo1 channels in human pulmonary arterial endothelial cells. Am J Physiol Cell Physiol 323:C959-c973. 10.1152/ajpcell.00313.2022 [DOI] [PMC free article] [PubMed] [Google Scholar]
316.Zheng J (2013) Molecular mechanism of TRP channels. Compr Physiol 3:221–242. 10.1002/cphy.c120001 [DOI] [PMC free article] [PubMed] [Google Scholar]
317.Zhou N, Lee JJ, Stoll S, Ma B, Costa KD, Qiu H (2017) Rho kinase regulates aortic vascular smooth muscle cell stiffness via Actin/SRF/Myocardin in hypertension. Cell Physiol Biochem 44:701–715. 10.1159/000485284 [DOI] [PMC free article] [PubMed] [Google Scholar]
318.Zhu MX, Tang J (2004) TRPC channel interactions with calmodulin and IP3 receptors. Novartis Found Symp 258:44–58 discussion 58-62, 98-102, 263-106 [PubMed] [Google Scholar]
319.Zou AP, Fleming JT, Falck JR, Jacobs ER, Gebremedhin D, Harder DR, Roman RJ (1996) 20-HETE is an endogenous inhibitor of the large-conductance Ca(2+)-activated K+ channel in renal arterioles. Am J Physiol 270:R228-237. 10.1152/ajpregu.1996.270.1.R228 [DOI] [PubMed] [Google Scholar]
320.Zou Y, Akazawa H, Qin Y, Sano M, Takano H, Minamino T, Makita N, Iwanaga K, Zhu W, Kudoh S, Toko H, Tamura K, Kihara M, Nagai T, Fukamizu A, Umemura S, Iiri T, Fujita T, Komuro I (2004) Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol 6:499–506. 10.1038/ncb1137 [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

No datasets were generated or analysed during the current study.

[CR1] 1.Adachi T (2010) Modulation of vascular sarco/endoplasmic reticulum calcium ATPase in cardiovascular pathophysiology. Adv Pharmacol 59:165–195. 10.1016/s1054-3589(10)59006-9 [DOI] [PubMed] [Google Scholar]

[CR2] 2.Alarcon-Martinez L, Yemisci M, Dalkara T (2021) Pericyte morphology and function. Histol Histopathol 36:633–643. 10.14670/hh-18-314 [DOI] [PubMed] [Google Scholar]

[CR3] 3.Alp NJ, McAteer MA, Khoo J, Choudhury RP, Channon KM (2004) Increased endothelial tetrahydrobiopterin synthesis by targeted transgenic GTP-cyclohydrolase I overexpression reduces endothelial dysfunction and atherosclerosis in ApoE-knockout mice. Arterioscler Thromb Vasc Biol 24:445–450. 10.1161/01.Atv.0000115637.48689.77 [DOI] [PubMed] [Google Scholar]

[CR4] 4.Álvarez-Santos MD, Álvarez-González M, Estrada-Soto S, Bazán-Perkins B (2020) Regulation of Myosin light-chain phosphatase activity to generate airway smooth muscle hypercontractility. Front Physiol 11:701. 10.3389/fphys.2020.00701 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR5] 5.Amberg GC, Navedo MF (2013) Calcium dynamics in vascular smooth muscle. Microcirculation 20:281–289. 10.1111/micc.12046 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR6] 6.Ambudkar IS, de Souza LB, Ong HL (2017) TRPC1, Orai1, and STIM1 in SOCE: Friends in tight spaces. Cell Calcium 63:33–39. 10.1016/j.ceca.2016.12.009 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR7] 7.Andrea JE, Walsh MP (1992) Protein kinase C of smooth muscle. Hypertension 20:585–595. 10.1161/01.hyp.20.5.585 [DOI] [PubMed] [Google Scholar]

[CR8] 8.Anwar MA, Shalhoub J, Lim CS, Gohel MS, Davies AH (2012) The effect of pressure-induced mechanical stretch on vascular wall differential gene expression. J Vasc Res 49:463–478. 10.1159/000339151 [DOI] [PubMed] [Google Scholar]

[CR9] 9.Anwar MA, Vorkas PA, Li J, Adesina-Georgiadis KN, Reslan OM, Raffetto JD, Want EJ, Khalil RA, Holmes E, Davies AH (2016) Prolonged mechanical circumferential stretch induces metabolic changes in rat inferior vena cava. Eur J Vasc Endovasc Surg 52:544–552. 10.1016/j.ejvs.2016.07.002 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR10] 10.Araki S, Ito M, Kureishi Y, Feng J, Machida H, Isaka N, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T (2001) Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase. Pflugers Arch 441:596–603. 10.1007/s004240000462 [DOI] [PubMed] [Google Scholar]

[CR11] 11.Arnaudeau S, Macrez-Leprêtre N, Mironneau J (1996) Activation of calcium sparks by angiotensin II in vascular myocytes. Biochem Biophys Res Commun 222:809–815. 10.1006/bbrc.1996.0808 [DOI] [PubMed] [Google Scholar]

[CR12] 12.Asunción-Alvarez D, Palacios J, Ybañez-Julca RO, Rodriguez-Silva CN, Nwokocha C, Cifuentes F, Greensmith DJ (2024) Calcium signaling in endothelial and vascular smooth muscle cells: sex differences and the influence of estrogens and androgens. Am J Physiol Heart Circ Physiol 326:H950-h970. 10.1152/ajpheart.00600.2023 [DOI] [PubMed] [Google Scholar]

[CR13] 13.Augustin HG, Koh GY (2024) A systems view of the vascular endothelium in health and disease. Cell 187:4833–4858. 10.1016/j.cell.2024.07.012 [DOI] [PubMed] [Google Scholar]

[CR14] 14.Austin C, Wray S (2000) Interactions between Ca(2+) and H(+) and functional consequences in vascular smooth muscle. Circ Res 86:355–363. 10.1161/01.res.86.3.355 [DOI] [PubMed] [Google Scholar]

[CR15] 15.Aviv A (1994) Cytosolic Ca2+, Na+/H+ antiport, protein kinase C trio in essential hypertension. Am J Hypertens 7:205–212. 10.1093/ajh/7.2.205 [DOI] [PubMed] [Google Scholar]

[CR16] 16.Balafanova Z, Bolli R, Zhang J, Zheng Y, Pass J, Bhatnagar A, Tang X-L, Wang O, Cardwell E, Ping P (2002) Nitric Oxide (NO) induces nitration of protein kinase Cε (PKCε), facilitating PKCε translocation via enhanced PKCε-RACK2 interactions. J Biol Chem 277:15021–15027 [DOI] [PubMed] [Google Scholar]

[CR17] 17.Beech DJ (2012) Orai1 calcium channels in the vasculature. Pflügers Arch Eur J Physiol 463:635–647. 10.1007/s00424-012-1090-2 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR18] 18.Belin de Chantemele EJ, Stepp DW (2012) Influence of obesity and metabolic dysfunction on the endothelial control in the coronary circulation. J Mol Cell Cardiol 52:840–847. 10.1016/j.yjmcc.2011.08.018 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR19] 19.Bergdahl A, Gomez MF, Wihlborg AK, Erlinge D, Eyjolfson A, Xu SZ, Beech DJ, Dreja K, Hellstrand P (2005) Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca2+ entry. Am J Physiol Cell Physiol 288:C872-880. 10.1152/ajpcell.00334.2004 [DOI] [PubMed] [Google Scholar]

[CR20] 20.Berlansky S, Humer C, Sallinger M, Frischauf I (2021) More than just simple interaction between STIM and Orai Proteins: CRAC channel function enabled by a network of interactions with regulatory proteins. Int J Mol Sci 22:471 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR21] 21.Berra-Romani R, Mazzocco-Spezzia A, Pulina MV, Golovina VA (2008) Ca2+ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture. Am J Physiol Cell Physiol 295:C779–C790. 10.1152/ajpcell.00173.2008 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR22] 22.Bertorello AM, Aperia A, Walaas SI, Nairn AC, Greengard P (1991) Phosphorylation of the catalytic subunit of Na+, K(+)-ATPase inhibits the activity of the enzyme. Proc Natl Acad Sci U S A 88:11359–11362. 10.1073/pnas.88.24.11359 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR23] 23.Bhullar SK, Shah AK, Dhalla NS (2019) Store-operated calcium channels: Potential target for the therapy of hypertension. Rev Cardiovasc Med 20:139–151. 10.31083/j.rcm.2019.03.522 [DOI] [PubMed] [Google Scholar]

[CR24] 24.Blatter LA (2017) Tissue specificity: SOCE: Implications for Ca(2+) handling in endothelial cells. Adv Exp Med Biol 993:343–361. 10.1007/978-3-319-57732-6_18 [DOI] [PubMed] [Google Scholar]

[CR25] 25.Boedtkjer E, Praetorius J, Matchkov VV, Stankevicius E, Mogensen S, Füchtbauer AC, Simonsen U, Füchtbauer EM, Aalkjaer C (2011) Disruption of Na+, HCO₃⁻ cotransporter NBCn1 (slc4a7) inhibits NO-mediated vasorelaxation, smooth muscle Ca2⁺ sensitivity, and hypertension development in mice. Circulation 124:1819–1829. 10.1161/circulationaha.110.015974 [DOI] [PubMed] [Google Scholar]

[CR26] 26.Bond M, Kitazawa T, Somlyo AP, Somlyo AV (1984) Release and recycling of calcium by the sarcoplasmic reticulum in guinea-pig portal vein smooth muscle. J Physiol 355:677–695. 10.1113/jphysiol.1984.sp015445 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR27] 27.Bourmeyster N, Vignais PV (1996) Phosphorylation of Rho GDI stabilizes the Rho A-Rho GDI complex in neutrophil cytosol. Biochem Biophys Res Commun 218:54–60. 10.1006/bbrc.1996.0011 [DOI] [PubMed] [Google Scholar]

[CR28] 28.Brayden JE, Earley S, Nelson MT, Reading S (2008) Transient receptor potential (TRP) channels, vascular tone and autoregulation of cerebral blood flow. Clin Exp Pharmacol Physiol 35:1116–1120. 10.1111/j.1440-1681.2007.04855.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR29] 29.Brescia P, Rescigno M (2021) The gut vascular barrier: a new player in the gut–liver–brain axis. Trends Mol Med 27:844–855. 10.1016/j.molmed.2021.06.007 [DOI] [PubMed] [Google Scholar]

[CR30] 30.Brueggemann LI, Mackie AR, Cribbs LL, Freda J, Tripathi A, Majetschak M, Byron KL (2014) Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of vascular Kv7 channels. J Biol Chem 289:2099–2111. 10.1074/jbc.M113.527820 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR31] 31.Callaghan B, Koh SD, Keef KD (2004) Muscarinic M2 receptor stimulation of Cav1.2b requires phosphatidylinositol 3-kinase, protein kinase C, and c-Src. Circ Res 94:626–633. 10.1161/01.Res.0000118248.17466.B7 [DOI] [PubMed] [Google Scholar]

[CR32] 32.Campinho P, Vilfan A, Vermot J (2020) Blood flow forces in shaping the vascular system: A focus on endothelial cell behavior. Front Physiol 11:552. 10.3389/fphys.2020.00552 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR33] 33.Cario-Toumaniantz C, Ferland-McCollough D, Chadeuf G, Toumaniantz G, Rodriguez M, Galizzi JP, Lockhart B, Bril A, Scalbert E, Loirand G, Pacaud P (2012) RhoA guanine exchange factor expression profile in arteries: evidence for a Rho kinase-dependent negative feedback in angiotensin II-dependent hypertension. Am J Physiol Cell Physiol 302:C1394-1404. 10.1152/ajpcell.00423.2011 [DOI] [PubMed] [Google Scholar]

[CR34] 34.Carroll MA, Garcia MP, Falck JR, McGiff JC (1992) Cyclooxygenase dependency of the renovascular actions of cytochrome P450-derived arachidonate metabolites. J Pharmacol Exp Ther 260:104–109 [PubMed] [Google Scholar]

[CR35] 35.Cartwright EJ, Oceandy D, Austin C, Neyses L (2011) Ca2+ signalling in cardiovascular disease: the role of the plasma membrane calcium pumps. Sci China Life Sci 54:691–698. 10.1007/s11427-011-4199-1 [DOI] [PubMed] [Google Scholar]

[CR36] 36.Castillo-Galán S, Arenas GA, Iturriaga R (2022) Contribution of STIM-activated TRPC-ORAI channels in pulmonary hypertension induced by chronic sustained and intermittent hypoxia. Curr Vasc Pharmacol 20:272–283. 10.2174/1570161120666220321141805 [DOI] [PubMed] [Google Scholar]

[CR37] 37.Ciavarella C, Motta I, Capri M, Gargiulo M, Pasquinelli G (2024) Heterogeneity and differentiation of the human arterial tree: Focus on microRNA expression in vascular disease. Biomolecules 14. 10.3390/biom14030343 [DOI] [PMC free article] [PubMed]

[CR38] 38.Cioffi DL (2011) Redox regulation of endothelial canonical transient receptor potential channels. Antioxid Redox Signal 15:1567–1582. 10.1089/ars.2010.3740 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR39] 39.Cioffi DL, Wu S, Chen H, Alexeyev M, St. Croix CM, Pitt BR, Uhlig S, Stevens T (2012) Orai1 determines calcium selectivity of an endogenous TRPC heterotetramer channel. Circulation Res 110:1435–1444. 10.1161/CIRCRESAHA.112.269506 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR40] 40.Cipolla MJ, Curry AB (2002) Middle cerebral artery function after stroke: the threshold duration of reperfusion for myogenic activity. Stroke 33:2094–2099. 10.1161/01.str.0000020712.84444.8d [DOI] [PubMed] [Google Scholar]

[CR41] 41.Clapham DE (2007) Calcium signaling. Cell 131:1047–1058. 10.1016/j.cell.2007.11.028 [DOI] [PubMed] [Google Scholar]

[CR42] 42.Collier ML, Ji G, Wang Y, Kotlikoff MI (2000) Calcium-induced calcium release in smooth muscle: loose coupling between the action potential and calcium release. J Gen Physiol 115:653–662. 10.1085/jgp.115.5.653 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR43] 43.Colyer J (1998) Phosphorylation states of phospholamban. Ann N Y Acad Sci 853:79–91. 10.1111/j.1749-6632.1998.tb08258.x [DOI] [PubMed] [Google Scholar]

[CR44] 44.Cox RH, Petrou S (1999) Ca(2+) influx inhibits voltage-dependent and augments Ca(2+)-dependent K(+) currents in arterial myocytes. Am J Physiol 277:C51-63. 10.1152/ajpcell.1999.277.1.C51 [DOI] [PubMed] [Google Scholar]

[CR45] 45.Cui Y, Gollasch M, Kassmann M (2023) Arterial myogenic response and aging. Ageing Res Rev 84:101813. 10.1016/j.arr.2022.101813 [DOI] [PubMed] [Google Scholar]

[CR46] 46.Cui Y, Kassmann M, Nickel S, Zhang C, Alenina N, Anistan YM, Schleifenbaum J, Bader M, Welsh DG, Huang Y, Gollasch M (2022) Myogenic vasoconstriction requires canonical G(q/11) signaling of the Angiotensin II type 1 receptor. J Am Heart Assoc 11:e022070. 10.1161/jaha.121.022070 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR47] 47.Cui Z, Zhang Y, Sheng L (2024) Targeting STIM1 contributes to alleviating remodeling of vascular smooth muscle cells in atherosclerosis. Discov Med 36:1678–1691. 10.24976/Discov.Med.202436187.154 [DOI] [PubMed] [Google Scholar]

[CR48] 48.Dedkova EN, Blatter LA (2002) Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum Ca2+ uptake in bovine vascular endothelial cells. J Physiol 539:77–91. 10.1113/jphysiol.2001.013258 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR49] 49.Dee RA, Mangum KD, Bai X, Mack CP, Taylor JM (2019) Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure. Pharmacol Ther 193:121–134. 10.1016/j.pharmthera.2018.09.001 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR50] 50.Deissler HL, Lang GE (2016) The protein kinase C inhibitor: Ruboxistaurin. Dev Ophthalmol 55:295–301. 10.1159/000431204 [DOI] [PubMed] [Google Scholar]

[CR51] 51.Dubois T, Oudinet JP, Mira JP, Russo-Marie F (1996) Annexins and protein kinases C. Biochim Biophys Acta 1313:290–294. 10.1016/0167-4889(96)00102-4 [DOI] [PubMed] [Google Scholar]

[CR52] 52.Dulhunty AF, Pouliquin P (2003) What we don’t know about the structure of ryanodine receptor calcium release channels. Clin Exp Pharmacol Physiol 30:713–723. 10.1046/j.1440-1681.2003.03904.x [DOI] [PubMed] [Google Scholar]

[CR53] 53.Dunaway LS, Mills WA 3rd, Eyo UB, Isakson BE (2025) The Cells of the vasculature: advances in the regulation of vascular tone in the brain and periphery. Basic Clin Pharmacol Toxicol 136:e70023. 10.1111/bcpt.70023 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR54] 54.Dupuis J, Hoeper MM (2008) Endothelin receptor antagonists in pulmonary arterial hypertension. Eur Respir J 31:407–415. 10.1183/09031936.00078207 [DOI] [PubMed] [Google Scholar]

[CR55] 55.Earley S, Brayden JE (2015) Transient receptor potential channels in the vasculature. Physiol Rev 95:645–690. 10.1152/physrev.00026.2014 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR56] 56.Eid AH (2025) A Game changer for resistant hypertension: The rise of aprocitentan. J Cardiovasc Pharmacol 85:312–315. 10.1097/fjc.0000000000001679 [DOI] [PubMed] [Google Scholar]

[CR57] 57.El Assar M, García-Rojo E, Sevilleja-Ortiz A, Sánchez-Ferrer A, Fernández A, García-Gómez B, Romero-Otero J, Rodríguez-Mañas L, Angulo J (2022) Functional role of STIM-1 and Orai1 in human microvascular aging. Cells 11. 10.3390/cells11223675 [DOI] [PMC free article] [PubMed]

[CR58] 58.Emrich SM, Yoast RE, Xin P, Arige V, Wagner LE, Hempel N, Gill DL, Sneyd J, Yule DI, Trebak M (2021) Omnitemporal choreographies of all five STIM/Orai and IP(3)Rs underlie the complexity of mammalian Ca(2+) signaling. Cell Rep 34:108760. 10.1016/j.celrep.2021.108760 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR59] 59.Evans AM (2017) Nanojunctions of the sarcoplasmic reticulum deliver site- and function-specific calcium signaling in vascular smooth muscles. Adv Pharmacol 78:1–47. 10.1016/bs.apha.2016.10.001 [DOI] [PubMed] [Google Scholar]

[CR60] 60.Evora PR, Cable DG, Chua YL, Rodrigues AJ, Pearson PJ, Schaff HV (2007) Nitric oxide and prostacyclin-dependent pathways involvement on in vitro induced hypothermia. Cryobiology 54:106–113. 10.1016/j.cryobiol.2006.12.002 [DOI] [PubMed] [Google Scholar]

[CR61] 61.Fan G, Cui Y, Gollasch M, Kassmann M (2019) Elementary calcium signaling in arterial smooth muscle. Channels (Austin) 13:505–519. 10.1080/19336950.2019.1688910 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR62] 62.Fang X, Faraci FM, Kaduce TL, Harmon S, Modrick ML, Hu S, Moore SA, Falck JR, Weintraub NL, Spector AA (2006) 20-Hydroxyeicosatetraenoic acid is a potent dilator of mouse basilar artery: role of cyclooxygenase. Am J Physiol Heart Circ Physiol 291:H2301-2307. 10.1152/ajpheart.00349.2006 [DOI] [PubMed] [Google Scholar]

[CR63] 63.Fantozzi I, Zhang S, Platoshyn O, Remillard CV, Cowling RT, Yuan JX (2003) Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 285:L1233-1245. 10.1152/ajplung.00445.2002 [DOI] [PubMed] [Google Scholar]

[CR64] 64.Félétou M, Verbeuren TJ, Vanhoutte PM (2009) Endothelium-dependent contractions in SHR: a tale of prostanoid TP and IP receptors. Br J Pharmacol 156:563–574. 10.1111/j.1476-5381.2008.00060.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR65] 65.Fill M, Copello JA (2002) Ryanodine receptor calcium release channels. Physiol Rev 82:893–922. 10.1152/physrev.00013.2002 [DOI] [PubMed] [Google Scholar]

[CR66] 66.Finkel T, Menazza S, Holmström KM, Parks RJ, Liu J, Sun J, Liu J, Pan X, Murphy E (2015) The ins and outs of mitochondrial calcium. Circ Res 116:1810–1819. 10.1161/circresaha.116.305484 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR67] 67.Fleissner F, Thum T (2011) Critical role of the nitric oxide/reactive oxygen species balance in endothelial progenitor dysfunction. Antioxid Redox Signal 15:933–948. 10.1089/ars.2010.3502 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR68] 68.Foote CA, Soares RN, Ramirez-Perez FI, Ghiarone T, Aroor A, Manrique-Acevedo C, Padilla J, Martinez-Lemus L (2022) Endothelial Glycocalyx. Compr Physiol 12:3781–3811. 10.1002/cphy.c210029 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR69] 69.Foskett JK, White C, Cheung KH, Mak DO (2007) Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev 87:593–658. 10.1152/physrev.00035.2006 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR70] 70.Fuloria M, Eckman DM, Leach DA, Aschner JL (2004) 20-hydroxyeicosatetraenoic acid is a vasoconstrictor in the newborn piglet pulmonary microcirculation. Am J Physiol Lung Cell Mol Physiol 287:L360-365. 10.1152/ajplung.00358.2003 [DOI] [PubMed] [Google Scholar]

[CR71] 71.Gao Y, Chen Z, Leung SW, Vanhoutte PM (2015) Hypoxic vasospasm mediated by cIMP: When soluble guanylyl cyclase turns bad. J Cardiovasc Pharmacol 65:545–548. 10.1097/fjc.0000000000000167 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR72] 72.Ghosh D, Syed AU, Prada MP, Nystoriak MA, Santana LF, Nieves-Cintrón M, Navedo MF (2017) Calcium channels in vascular smooth muscle. Adv Pharmacol 78:49–87. 10.1016/bs.apha.2016.08.002 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR73] 73.Giachini FR, Chiao CW, Carneiro FS, Lima VV, Carneiro ZN, Dorrance AM, Tostes RC, Webb RC (2009) Increased activation of stromal interaction molecule-1/Orai-1 in aorta from hypertensive rats: a novel insight into vascular dysfunction. Hypertension 53:409–416. 10.1161/hypertensionaha.108.124404 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR74] 74.Giachini FR, Webb RC, Tostes RC (2009) STIM and Orai proteins: players in sexual differences in hypertension-associated vascular dysfunction? Clin Sci (Lond) 118:391–396. 10.1042/cs20090449 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR75] 75.Gilbert-Honick J, Grayson W (2020) Vascularized and innervated skeletal muscle tissue engineering. Adv Healthc Mater 9:e1900626. 10.1002/adhm.201900626 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR76] 76.Glavind-Kristensen M, Matchkov V, Hansen VB, Forman A, Nilsson H, Aalkjaer C (2004) KATP-channel-induced vasodilation is modulated by the Na,K-pump activity in rabbit coronary small arteries. Br J Pharmacol 143:872–880. 10.1038/sj.bjp.0706016 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR77] 77.Gluais P, Lonchampt M, Morrow JD, Vanhoutte PM, Feletou M (2005) Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin. Br J Pharmacol 146:834–845. 10.1038/sj.bjp.0706390 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR78] 78.Gluais P, Paysant J, Badier-Commander C, Verbeuren T, Vanhoutte PM, Félétou M (2006) In SHR aorta, calcium ionophore A-23187 releases prostacyclin and thromboxane A2 as endothelium-derived contracting factors. Am J Physiol Heart Circ Physiol 291:H2255-2264. 10.1152/ajpheart.01115.2005 [DOI] [PubMed] [Google Scholar]

[CR79] 79.Goddard J, Webb DJ (2000) Plasma endothelin concentrations in hypertension. J Cardiovasc Pharmacol 35:S25-31. 10.1097/00005344-200000002-00007 [DOI] [PubMed] [Google Scholar]

[CR80] 80.Gollasch M (2012) Vasodilator signals from perivascular adipose tissue. Br J Pharmacol 165:633–642. 10.1111/j.1476-5381.2011.01430.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR81] 81.Gollasch M (2017) Adipose-vascular coupling and potential therapeutics. Annu Rev Pharmacol Toxicol 57:417–436. 10.1146/annurev-pharmtox-010716-104542 [DOI] [PubMed] [Google Scholar]

[CR82] 82.Gong MC, Fuglsang A, Alessi D, Kobayashi S, Cohen P, Somlyo AV, Somlyo AP (1992) Arachidonic acid inhibits myosin light chain phosphatase and sensitizes smooth muscle to calcium. J Biol Chem 267:21492–21498 [PubMed] [Google Scholar]

[CR83] 83.Gong MC, Fujihara H, Somlyo AV, Somlyo AP (1997) Translocation of rhoA associated with Ca2+ sensitization of smooth muscle. J Biol Chem 272:10704–10709. 10.1074/jbc.272.16.10704 [DOI] [PubMed] [Google Scholar]

[CR84] 84.Gopalakrishna R, Anderson WB (1989) Ca2+- and phospholipid-independent activation of protein kinase C by selective oxidative modification of the regulatory domain. Proc Natl Acad Sci U S A 86:6758–6762. 10.1073/pnas.86.17.6758 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR85] 85.Grange JJ, Baca-Regen LM, Nollendorfs AJ, Persidsky Y, Sudan DL, Baxter BT (1998) Protein kinase C isoforms in human aortic smooth muscle cells. J Vasc Surg 27:919–926. 10.1016/s0741-5214(98)70273-3. discussion 926-917 [DOI] [PubMed] [Google Scholar]

[CR86] 86.Griendling KK, Rittenhouse SE, Brock TA, Ekstein LS, Gimbrone MA Jr, Alexander RW (1986) Sustained diacylglycerol formation from inositol phospholipids in angiotensin II-stimulated vascular smooth muscle cells. J Biol Chem 261:5901–5906 [PubMed] [Google Scholar]

[CR87] 87.Grubb S, Lauritzen M, Aalkjær C (2021) Brain capillary pericytes and neurovascular coupling. Comp Biochem Physiol A: Mol Integr Physiol 254:110893. 10.1016/j.cbpa.2020.110893 [DOI] [PubMed] [Google Scholar]

[CR88] 88.Grunz E, Jones B, Lateef O, Sen S, Wilkenson K, Joshi T, Boerman EM (2023) Adventitial macrophage accumulation impairs perivascular nerve function in mesenteric arteries with inflammatory bowel disease. bioRxiv. 10.1101/2023.04.04.535591 [DOI] [PMC free article] [PubMed]

[CR89] 89.Guerrero-Hernández A, Gómez-Viquez L, Guerrero-Serna G, Rueda A (2002) Ryanodine receptors in smooth muscle. Front Biosci 7:d1676-1688. 10.2741/a871 [DOI] [PubMed] [Google Scholar]

[CR90] 90.Halvorson BD, Ahmed M, Huang SJ, Frisbee JC (2024) Scoping review: integration of the major mechanisms underlying the regulation of arteriolar tone. J Vasc Res 61:1–15. 10.1159/000535404 [DOI] [PubMed] [Google Scholar]

[CR91] 91.Hamilton SL, Serysheva II (2009) Ryanodine receptor structure: progress and challenges. J Biol Chem 284:4047–4051. 10.1074/jbc.R800054200 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR92] 92.Harraz OF, Jensen LJ (2021) Vascular calcium signalling and ageing. J Physiol 599:5361–5377. 10.1113/jp280950 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR93] 93.Hartmann J, Dragicevic E, Adelsberger H, Henning HA, Sumser M, Abramowitz J, Blum R, Dietrich A, Freichel M, Flockerzi V, Birnbaumer L, Konnerth A (2008) TRPC3 channels are required for synaptic transmission and motor coordination. Neuron 59:392–398. 10.1016/j.neuron.2008.06.009 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR94] 94.Hartmann S, Ridley A, Lutz S (2015) The function of rho-associated kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease. Front Pharmacol 6. 10.3389/fphar.2015.00276 [DOI] [PMC free article] [PubMed]

[CR95] 95.Hashad AM, Harraz OF, Brett SE, Romero M, Kassmann M, Puglisi JL, Wilson SM, Gollasch M, Welsh DG (2018) Caveolae link Ca(V)3.2 channels to BK(Ca)-Mediated feedback in vascular smooth muscle. Arterioscler Thromb Vasc Biol 38:2371–2381. 10.1161/atvbaha.118.311394 [DOI] [PubMed] [Google Scholar]

[CR96] 96.Heiss EH, Dirsch VM (2014) Regulation of eNOS enzyme activity by posttranslational modification. Curr Pharm Des 20:3503–3513. 10.2174/13816128113196660745 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR97] 97.Hiley E, McMullan R, Nurrish SJ (2006) The Galpha12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in C. elegans. Embo j 25:5884–5895. 10.1038/sj.emboj.7601458 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR98] 98.Hill-Eubanks DC, Werner ME, Heppner TJ, Nelson MT (2011) Calcium signaling in smooth muscle. Cold Spring Harb Perspect Biol 3:a004549. 10.1101/cshperspect.a004549 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR99] 99.Hill BJ, Muldrew E (2014) Oestrogen upregulates the sarcoplasmic reticulum Ca(2+) ATPase pump in coronary arteries. Clin Exp Pharmacol Physiol 41:430–436. 10.1111/1440-1681.12233 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR100] 100.Hill BJF, Dalton RJ, Joseph BK, Thakali KM, Rusch NJ (2017) 17β-estradiol reduces Ca(v) 1.2 channel abundance and attenuates Ca(2+) -dependent contractions in coronary arteries. Pharmacol Res Perspect 5. 10.1002/prp2.358 [DOI] [PMC free article] [PubMed]

[CR101] 101.Hill MA, Meininger GA (2016) Small artery mechanobiology: Roles of cellular and non-cellular elements. Microcirculation 23:611–613. 10.1111/micc.12323 [DOI] [PubMed] [Google Scholar]

[CR102] 102.Hoefer IE, den Adel B, Daemen MJ (2013) Biomechanical factors as triggers of vascular growth. Cardiovasc Res 99:276–283. 10.1093/cvr/cvt089 [DOI] [PubMed] [Google Scholar]

[CR103] 103.Hofmann T, Chubanov V, Gudermann T, Montell C (2003) TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective cation channel. Curr Biol 13:1153–1158. 10.1016/s0960-9822(03)00431-7 [DOI] [PubMed] [Google Scholar]

[CR104] 104.Hoopes SL, Garcia V, Edin ML, Schwartzman ML, Zeldin DC (2015) Vascular actions of 20-HETE. Prostaglandins Other Lipid Mediat 120:9–16. 10.1016/j.prostaglandins.2015.03.002 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR105] 105.Hou X, Roberts LJ 2nd, Gobeil F Jr, Taber D, Kanai K, Abran D, Brault S, Checchin D, Sennlaub F, Lachapelle P, Varma D, Chemtob S (2004) Isomer-specific contractile effects of a series of synthetic f2-isoprostanes on retinal and cerebral microvasculature. Free Radic Biol Med 36:163–172. 10.1016/j.freeradbiomed.2003.10.024 [DOI] [PubMed] [Google Scholar]

[CR106] 106.Hübner CA, Schroeder BC, Ehmke H (2015) Regulation of vascular tone and arterial blood pressure: role of chloride transport in vascular smooth muscle. Pflugers Arch 467:605–614. 10.1007/s00424-014-1684-y [DOI] [PubMed] [Google Scholar]

[CR107] 107.Huveneers S, Daemen MJ, Hordijk PL (2015) Between Rho(k) and a hard place: the relation between vessel wall stiffness, endothelial contractility, and cardiovascular disease. Circ Res 116:895–908. 10.1161/circresaha.116.305720 [DOI] [PubMed] [Google Scholar]

[CR108] 108.Chakraborty S, Deb BK, Chorna T, Konieczny V, Taylor CW, Hasan G (2016) Mutant IP3 receptors attenuate store-operated Ca2+ entry by destabilizing STIM-Orai interactions in Drosophila neurons. J Cell Sci 129:3903–3910. 10.1242/jcs.191585 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR109] 109.Chen Z, Zhang X, Ying L, Dou D, Li Y, Bai Y, Liu J, Liu L, Feng H, Yu X, Leung SW, Vanhoutte PM, Gao Y (2014) cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries. Am J Physiol Heart Circ Physiol 307:H328-336. 10.1152/ajpheart.00132.2014 [DOI] [PubMed] [Google Scholar]

[CR110] 110.Cheng H, Lederer WJ, Cannell MB (1993) Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science 262:740–744. 10.1126/science.8235594 [DOI] [PubMed] [Google Scholar]

[CR111] 111.Choi H, Tostes RC, Webb RC (2011) S-nitrosylation Inhibits protein kinase C-mediated contraction in mouse aorta. J Cardiovasc Pharmacol 57:65–71. 10.1097/FJC.0b013e3181fef9cb [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR112] 112.Inagaki M, Yokokura H, Itoh T, Kanmura Y, Kuriyama H, Hidaka H (1987) Purified rabbit brain protein kinase C relaxes skinned vascular smooth muscle and phosphorylates myosin light chain. Arch Biochem Biophys 254:136–141. 10.1016/0003-9861(87)90089-0 [DOI] [PubMed] [Google Scholar]

[CR113] 113.Inoue R, Jensen LJ, Jian Z, Shi J, Hai L, Lurie AI, Henriksen FH, Salomonsson M, Morita H, Kawarabayashi Y, Mori M, Mori Y, Ito Y (2009) Synergistic activation of vascular TRPC6 channel by receptor and mechanical stimulation via phospholipase C/diacylglycerol and phospholipase A2/omega-hydroxylase/20-HETE pathways. Circ Res 104:1399–1409. 10.1161/circresaha.108.193227 [DOI] [PubMed] [Google Scholar]

[CR114] 114.Isakson BE, Ramos SI, Duling BR (2007) Ca2+ and inositol 1,4,5-trisphosphate-mediated signaling across the myoendothelial junction. Circ Res 100:246–254. 10.1161/01.Res.0000257744.23795.93 [DOI] [PubMed] [Google Scholar]

[CR115] 115.Ito K, Hirooka Y, Kimura Y, Shimokawa H, Takeshita A (2005) Effects of hydroxyfasudil administered to the nucleus tractus solitarii on blood pressure and heart rate in spontaneously hypertensive rats. Clin Exp Hypertens 27:269–277 [PubMed] [Google Scholar]

[CR116] 116.Ito K, Hirooka Y, Sakai K, Kishi T, Kaibuchi K, Shimokawa H, Takeshita A (2003) Rho/Rho-kinase pathway in brain stem contributes to blood pressure regulation via sympathetic nervous system: possible involvement in neural mechanisms of hypertension. Circ Res 92:1337–1343. 10.1161/01.Res.0000079941.59846.D4 [DOI] [PubMed] [Google Scholar]

[CR117] 117.Jaggar JH, Porter VA, Lederer WJ, Nelson MT (2000) Calcium sparks in smooth muscle. Am J Physiol Cell Physiol 278:C235-256. 10.1152/ajpcell.2000.278.2.C235 [DOI] [PubMed] [Google Scholar]

[CR118] 118.Jaggar JH, Wellman GC, Heppner TJ, Porter VA, Perez GJ, Gollasch M, Kleppisch T, Rubart M, Stevenson AS, Lederer WJ, Knot HJ, Bonev AD, Nelson MT (1998) Ca2+ channels, ryanodine receptors and Ca(2+)-activated K+ channels: a functional unit for regulating arterial tone. Acta Physiol Scand 164:577–587. 10.1046/j.1365-201X.1998.00462.x [DOI] [PubMed] [Google Scholar]

[CR119] 119.Jankowich M, Choudhary G (2020) Endothelin-1 levels and cardiovascular events. Trends Cardiovasc Med 30:1–8. 10.1016/j.tcm.2019.01.007 [DOI] [PubMed] [Google Scholar]

[CR120] 120.Je HD, Gangopadhyay SS, Ashworth TD, Morgan KG (2001) Calponin is required for agonist-induced signal transduction–evidence from an antisense approach in ferret smooth muscle. J Physiol 537:567–577. 10.1111/j.1469-7793.2001.00567.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR121] 121.Jho D, Mehta D, Ahmmed G, Gao X-P, Tiruppathi C, Broman M, Malik AB (2005) Angiopoietin-1 Opposes VEGF-Induced Increase in Endothelial Permeability by Inhibiting TRPC1-Dependent Ca2 Influx. Circ Res 96:1282–1290. 10.1161/01.RES.0000171894.03801.03 [DOI] [PubMed] [Google Scholar]

[CR122] 122.Johnson JA, Barman SA (2004) Protein kinase C modulation of cyclic GMP in rat neonatal pulmonary vascular smooth muscle. Lung 182:79–89. 10.1007/s00408-003-1046-6 [DOI] [PubMed] [Google Scholar]

[CR123] 123.Joyner MJ, Wallin BG, Charkoudian N (2016) Sex differences and blood pressure regulation in humans. Exp Physiol 101:349–355. 10.1113/ep085146 [DOI] [PubMed] [Google Scholar]

[CR124] 124.Jufri NF, Mohamedali A, Avolio A, Baker MS (2015) Mechanical stretch: physiological and pathological implications for human vascular endothelial cells. Vasc Cell 7:8. 10.1186/s13221-015-0033-z [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR125] 125.Kaneko T, Amano M, Maeda A, Goto H, Takahashi K, Ito M, Kaibuchi K (2000) Identification of calponin as a novel substrate of Rho-kinase. Biochem Biophys Res Commun 273:110–116. 10.1006/bbrc.2000.2901 [DOI] [PubMed] [Google Scholar]

[CR126] 126.Katada T, Gilman AG, Watanabe Y, Bauer S, Jakobs KH (1985) Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur J Biochem 151:431–437. 10.1111/j.1432-1033.1985.tb09120.x [DOI] [PubMed] [Google Scholar]

[CR127] 127.Katusic ZS, Shepherd JT, Vanhoutte PM (1987) Endothelium-dependent contraction to stretch in canine basilar arteries. Am J Physiol 252:H671-673. 10.1152/ajpheart.1987.252.3.H671 [DOI] [PubMed] [Google Scholar]

[CR128] 128.Kawasaki H, Takatori S, Zamami Y, Koyama T, Goda M, Hirai K, Tangsucharit P, Jin X, Hobara N, Kitamura Y (2011) Paracrine control of mesenteric perivascular axo-axonal interaction. Acta Physiol (Oxf) 203:3–11. 10.1111/j.1748-1716.2010.02197.x [DOI] [PubMed] [Google Scholar]

[CR129] 129.Khaddaj Mallat R, Mathew John C, Kendrick DJ, Braun AP (2017) The vascular endothelium: A regulator of arterial tone and interface for the immune system. Crit Rev Clin Lab Sci 54:458–470. 10.1080/10408363.2017.1394267 [DOI] [PubMed] [Google Scholar]

[CR130] 130.Kikkawa U, Takai Y, Tanaka Y, Miyake R, Nishizuka Y (1983) Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters. J Biol Chem 258:11442–11445 [PubMed] [Google Scholar]

[CR131] 131.Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG (2008) Smooth muscle signalling pathways in health and disease. J Cell Mol Med 12:2165–2180. 10.1111/j.1582-4934.2008.00552.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR132] 132.Kim HR, Gallant C, Morgan KG (2013) Regulation of PKC autophosphorylation by calponin in contractile vascular smooth muscle tissue. Biomed Res Int 2013:358643. 10.1155/2013/358643 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR133] 133.Kim HR, Gallant C, Morgan KG (2013) Regulation of PKC autophosphorylation by calponin in contractile vascular smooth muscle tissue. Biomed Res Int 2013:358643–358643. 10.1155/2013/358643 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR134] 134.Kitazawa T, Eto M, Woodsome TP, Brautigan DL (2000) Agonists trigger G protein-mediated activation of the CPI-17 inhibitor phosphoprotein of myosin light chain phosphatase to enhance vascular smooth muscle contractility. J Biol Chem 275:9897–9900. 10.1074/jbc.275.14.9897 [DOI] [PubMed] [Google Scholar]

[CR135] 135.Kitazawa T, Kitazawa K (2012) Size-dependent heterogeneity of contractile Ca2+ sensitization in rat arterial smooth muscle. J Physiol 590:5401–5423. 10.1113/jphysiol.2012.241315 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR136] 136.Knot HJ, Nelson MT (1998) Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure. J Physiol 508(Pt 1):199–209. 10.1111/j.1469-7793.1998.199br.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR137] 137.Kold-Petersen H, Brøndum E, Nilsson H, Flyvbjerg A, Aalkjaer C (2012) Impaired myogenic tone in isolated cerebral and coronary resistance arteries from the goto-kakizaki rat model of type 2 diabetes. J Vasc Res 49:267–278. 10.1159/000335487 [DOI] [PubMed] [Google Scholar]

[CR138] 138.Kolettis TM, Barton M, Langleben D, Matsumura Y (2013) Endothelin in coronary artery disease and myocardial infarction. Cardiol Rev 21:249–256. 10.1097/CRD.0b013e318283f65a [DOI] [PubMed] [Google Scholar]

[CR139] 139.Kozai D, Ogawa N, Mori Y (2014) Redox regulation of transient receptor potential channels. Antioxid Redox Signal 21:971–986. 10.1089/ars.2013.5616 [DOI] [PubMed] [Google Scholar]

[CR140] 140.Kur J, Bankhead P, Scholfield CN, Curtis TM, McGeown JG (2013) Ca(2+) sparks promote myogenic tone in retinal arterioles. Br J Pharmacol 168:1675–1686. 10.1111/bph.12044 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR141] 141.Lacruz RS, Feske S (2015) Diseases caused by mutations in ORAI1 and STIM1. Ann N Y Acad Sci 1356:45–79. 10.1111/nyas.12938 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR142] 142.Laffin LJ, Bakris GL (2015) Endothelin antagonism and hypertension: an evolving target. Semin Nephrol 35:168–175. 10.1016/j.semnephrol.2015.03.001 [DOI] [PubMed] [Google Scholar]

[CR143] 143.Lagaud GJ, Skarsgard PL, Laher I, van Breemen C (1999) Heterogeneity of endothelium-dependent vasodilation in pressurized cerebral and small mesenteric resistance arteries of the rat. J Pharmacol Exp Ther 290:832–839 [PubMed] [Google Scholar]

[CR144] 144.Lamping KG, Wess J, Cui Y, Nuno DW, Faraci FM (2004) Muscarinic (M) receptors in coronary circulation: gene-targeted mice define the role of M2 and M3 receptors in response to acetylcholine. Arterioscler Thromb Vasc Biol 24:1253–1258. 10.1161/01.ATV.0000130661.82773.ca [DOI] [PubMed] [Google Scholar]

[CR145] 145.Lanner JT, Georgiou DK, Joshi AD, Hamilton SL (2010) Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol 2:a003996. 10.1101/cshperspect.a003996 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR146] 146.Lanza GA, Shimokawa H (2023) Management of Coronary Artery Spasm. Eur Cardiol 18:e38. 10.15420/ecr.2022.47 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR147] 147.Large WA, Wang Q (1996) Characteristics and physiological role of the Ca(2+)-activated Cl- conductance in smooth muscle. Am J Physiol 271:C435-454. 10.1152/ajpcell.1996.271.2.C435 [DOI] [PubMed] [Google Scholar]

[CR148] 148.Laufs U, Liao JK (1998) Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 273:24266–24271. 10.1074/jbc.273.37.24266 [DOI] [PubMed] [Google Scholar]

[CR149] 149.Launay P, Fleig A, Perraud AL, Scharenberg AM, Penner R, Kinet JP (2002) TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization. Cell 109:397–407. 10.1016/s0092-8674(02)00719-5 [DOI] [PubMed] [Google Scholar]

[CR150] 150.Laver DR (2018) Regulation of the RyR channel gating by Ca(2+) and Mg(2). Biophys Rev 10:1087–1095. 10.1007/s12551-018-0433-4 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR151] 151.LeCouter J, Moritz DR, Li B, Phillips GL, Liang XH, Gerber HP, Hillan KJ, Ferrara N (2003) Angiogenesis-independent endothelial protection of liver: role of VEGFR-1. Science 299:890–893. 10.1126/science.1079562 [DOI] [PubMed] [Google Scholar]

[CR152] 152.Ledoux J, Gee DM, Leblanc N (2003) Increased peripheral resistance in heart failure: new evidence suggests an alteration in vascular smooth muscle function. Br J Pharmacol 139:1245–1248. 10.1038/sj.bjp.0705366 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR153] 153.Ledoux J, Werner ME, Brayden JE, Nelson MT (2006) Calcium-activated potassium channels and the regulation of vascular tone. Physiology (Bethesda) 21:69–78. 10.1152/physiol.00040.2005 [DOI] [PubMed] [Google Scholar]

[CR154] 154.Li T, Thoen ZE, Applebaum JM, Khalil RA (2025) Menopause-related changes in vascular signaling by sex hormones. J Pharmacol Exp Ther 392:103526. 10.1016/j.jpet.2025.103526 [DOI] [PubMed] [Google Scholar]

[CR155] 155.Li T, Yang GM, Zhu Y, Wu Y, Chen XY, Lan D, Tian KL, Liu LM (2015) Diabetes and hyperlipidemia induce dysfunction of VSMCs: contribution of the metabolic inflammation/miRNA pathway. Am J Physiol Endocrinol Metab 308:E257-269. 10.1152/ajpendo.00348.2014 [DOI] [PubMed] [Google Scholar]

[CR156] 156.Li W, Zhu K, Liu Y, Liu M, Chen Q (2025) Recent advances in PKC inhibitor development: Structural design strategies and therapeutic applications. Eur J Med Chem 287:117290. 10.1016/j.ejmech.2025.117290 [DOI] [PubMed] [Google Scholar]

[CR157] 157.Li X, Zhao G, Ma B, Li R, Hong J, Liu S, Wang DW (2014) 20-Hydroxyeicosatetraenoic acid impairs endothelial insulin signaling by inducing phosphorylation of the insulin receptor substrate-1 at Ser616. PLoS One 9:e95841. 10.1371/journal.pone.0095841 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR158] 158.Liang CF, Liu JT, Wang Y, Xu A, Vanhoutte PM (2013) Toll-like receptor 4 mutation protects obese mice against endothelial dysfunction by decreasing NADPH oxidase isoforms 1 and 4. Arterioscler Thromb Vasc Biol 33:777–784. 10.1161/atvbaha.112.301087 [DOI] [PubMed] [Google Scholar]

[CR159] 159.Lillestłl IK, Helle KB, Aardal S (1998) Relaxing effects of cyclic GMP and cyclic AMP-enhancing agents on the long-lasting contraction to endothelin-1 in the porcine coronary artery. Scand J Clin Lab Invest 58:625–634. 10.1080/00365519850186058 [DOI] [PubMed] [Google Scholar]

[CR160] 160.Lindsey SH, Liu L, Chappell MC (2014) Vasodilation by GPER in mesenteric arteries involves both endothelial nitric oxide and smooth muscle cAMP signaling. Steroids 81:99–102. 10.1016/j.steroids.2013.10.017 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR161] 161.Liu X, Luo D, Zhang J, Du L (2020) Distribution and relative expression of vasoactive receptors on arteries. Sci Rep 10:15383. 10.1038/s41598-020-72352-5 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR162] 162.Liu Z, Khalil RA (2018) Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease. Biochem Pharmacol 153:91–122. 10.1016/j.bcp.2018.02.012 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR163] 163.Loirand G (2015) Rho kinases in health and disease: From basic science to translational research. Pharmacol Rev 67:1074–1095. 10.1124/pr.115.010595 [DOI] [PubMed] [Google Scholar]

[CR164] 164.Loirand G, Guilluy C, Pacaud P (2006) Regulation of Rho proteins by phosphorylation in the cardiovascular system. Trends Cardiovasc Med 16:199–204. 10.1016/j.tcm.2006.03.010 [DOI] [PubMed] [Google Scholar]

[CR165] 165.Longden TA, Isaacs D (2025) Pericyte electrical signalling and brain haemodynamics. Basic Clin Pharmacol Toxicol 136:e70030. 10.1111/bcpt.70030 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR166] 166.Lopez JJ, Jardin I, Sanchez-Collado J, Salido GM, Smani T, Rosado JA (2020) TRPC channels in the SOCE Scenario. Cells 9(1). 10.3390/cells9010126 [DOI] [PMC free article] [PubMed]

[CR167] 167.Lu D, Kassab GS (2011) Role of shear stress and stretch in vascular mechanobiology. J R Soc Interface 8:1379–1385. 10.1098/rsif.2011.0177 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR168] 168.Lu X, Kassab GS (2015) Integrins mediate mechanical compression-induced endothelium-dependent vasodilation through endothelial nitric oxide pathway. J Gen Physiol 146:221–232. 10.1085/jgp.201411350 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR169] 169.Luykenaar KD, Brett SE, Wu BN, Wiehler WB, Welsh DG (2004) Pyrimidine nucleotides suppress KDR currents and depolarize rat cerebral arteries by activating Rho kinase. Am J Physiol-Heart Circulatory Physiol 286:H1088–H1100. 10.1152/ajpheart.00903.2003 [DOI] [PubMed] [Google Scholar]

[CR170] 170.Ma MM, Gao M, Guo KM, Wang M, Li XY, Zeng XL, Sun L, Lv XF, Du YH, Wang GL, Zhou JG, Guan YY (2017) TMEM16A Contributes to endothelial dysfunction by facilitating Nox2 NADPH oxidase-derived reactive oxygen species generation in hypertension. Hypertension 69:892–901. 10.1161/hypertensionaha.116.08874 [DOI] [PubMed] [Google Scholar]

[CR171] 171.Mao Y, Su J, Lei L, Meng L, Qi Y, Huo Y, Tang C (2014) Adrenomedullin and adrenotensin increase the transcription of regulator of G-protein signaling 2 in vascular smooth muscle cells via the cAMP-dependent and PKC pathways. Mol Med Rep 9:323–327. 10.3892/mmr.2013.1751 [DOI] [PubMed] [Google Scholar]

[CR172] 172.Martín-Aragón Baudel MAS, Shi J, Large WA, Albert AP (2020) Insights into activation mechanisms of store-operated TRPC1 channels in vascular smooth muscle. Cells 9:179 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR173] 173.Maruhashi T, Higashi Y (2021) An overview of pharmacotherapy for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage. Expert Opin Pharmacother 22:1601–1614. 10.1080/14656566.2021.1912013 [DOI] [PubMed] [Google Scholar]

[CR174] 174.Mather KJ, Mirzamohammadi B, Lteif A, Steinberg HO, Baron AD (2002) Endothelin contributes to basal vascular tone and endothelial dysfunction in human obesity and type 2 diabetes. Diabetes 51:3517–3523. 10.2337/diabetes.51.12.3517 [DOI] [PubMed] [Google Scholar]

[CR175] 175.Matchkov VV, Gustafsson H, Rahman A, Briggs Boedtkjer DM, Gorintin S, Hansen AK, Bouzinova EV, Praetorius HA, Aalkjaer C, Nilsson H (2007) Interaction between Na+/K+-pump and Na+/Ca2+-exchanger modulates intercellular communication. Circ Res 100:1026–1035. 10.1161/01.Res.0000262659.09293.56 [DOI] [PubMed] [Google Scholar]

[CR176] 176.Matchkov VV, Krivoi II (2016) Specialized functional diversity and interactions of the Na. K-ATPase Front Physiol 7:179. 10.3389/fphys.2016.00179 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR177] 177.Matsubara H, Hogan DE, Morgan EF, Mortlock DP, Einhorn TA, Gerstenfeld LC (2012) Vascular tissues are a primary source of BMP2 expression during bone formation induced by distraction osteogenesis. Bone 51:168–180. 10.1016/j.bone.2012.02.017 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR178] 178.Matsui T, Maeda M, Doi Y, Yonemura S, Amano M, Kaibuchi K, Tsukita S, Tsukita S (1998) Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association. J Cell Biol 140:647–657. 10.1083/jcb.140.3.647 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR179] 179.Mbikou P, Fajmut A, Brumen M, Roux E (2011) Contribution of Rho kinase to the early phase of the calcium-contraction coupling in airway smooth muscle. Exp Physiol 96:240–258. 10.1113/expphysiol.2010.054635 [DOI] [PubMed] [Google Scholar]

[CR180] 180.Mederos y Schnitzler M, Storch U, Meibers S, Nurwakagari P, Breit A, Essin K, Gollasch M, Gudermann T (2008) Gq-coupled receptors as mechanosensors mediating myogenic vasoconstriction. Embo J 27:3092–3103. 10.1038/emboj.2008.233 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR181] 181.Meens MJ, Mattheij NJ, van Loenen PB, Spijkers LJ, Lemkens P, Nelissen J, Compeer MG, Alewijnse AE, De Mey JG (2012) G-protein βγ subunits in vasorelaxing and anti-endothelinergic effects of calcitonin gene-related peptide. Br J Pharmacol 166:297–308. 10.1111/j.1476-5381.2011.01774.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR182] 182.Meissner G (2017) The structural basis of ryanodine receptor ion channel function. J Gen Physiol 149:1065–1089. 10.1085/jgp.201711878 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR183] 183.Mendonça MC, Koles N, Sellitti DF (2012) Protein kinase C-δ (PKC-δ) and PKC-α mediate Ca(2+)-dependent increases in CNP mRNA in human vascular cells. Vascul Pharmacol 57:98–104. 10.1016/j.vph.2012.05.002 [DOI] [PubMed] [Google Scholar]

[CR184] 184.Miao LN, Pan D, Shi J, Du JP, Chen PF, Gao J, Yu Y, Shi DZ, Guo M (2022) Role and mechanism of PKC-δ for cardiovascular disease: Current status and perspective. Front Cardiovasc Med 9:816369. 10.3389/fcvm.2022.816369 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR185] 185.Miller BA, Zhang W (2011) TRP channels as mediators of oxidative stress. Adv Exp Med Biol 704:531–544. 10.1007/978-94-007-0265-3_29 [DOI] [PubMed] [Google Scholar]

[CR186] 186.Minami K, Fukuzawa K, Nakaya Y (1993) Protein kinase C inhibits the Ca(2+)-activated K+ channel of cultured porcine coronary artery smooth muscle cells. Biochem Biophys Res Commun 190:263–269. 10.1006/bbrc.1993.1040 [DOI] [PubMed] [Google Scholar]

[CR187] 187.Ming XF, Barandier C, Viswambharan H, Kwak BR, Mach F, Mazzolai L, Hayoz D, Ruffieux J, Rusconi S, Montani JP, Yang Z (2004) Thrombin stimulates human endothelial arginase enzymatic activity via RhoA/ROCK pathway: implications for atherosclerotic endothelial dysfunction. Circulation 110:3708–3714. 10.1161/01.Cir.0000142867.26182.32 [DOI] [PubMed] [Google Scholar]

[CR188] 188.Mironova GY, Kowalewska PM, El-Lakany M, Tran CHT, Sancho M, Zechariah A, Jackson WF, Welsh DG (2023) The conducted vasomotor response and the principles of electrical communication in resistance arteries. Physiol Rev 104:33–84. 10.1152/physrev.00035.2022 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR189] 189.Mitsui R, Hashitani H (2020) Synchrony of spontaneous Ca(2+) activity in microvascular mural cells. J Smooth Muscle Res 56:1–18. 10.1540/jsmr.56.1 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR190] 190.Moccia F, Brunetti V, Perna A, Guerra G, Soda T, Berra-Romani R (2023) The molecular heterogeneity of store-operated Ca(2+) entry in vascular endothelial cells: The different roles of Orai1 and TRPC1/TRPC4 channels in the transition from Ca(2+)-selective to non-selective cation currents. Int J Mol Sci 24. 10.3390/ijms24043259 [DOI] [PMC free article] [PubMed]

[CR191] 191.Moccia F, Negri S, Faris P, Berra-Romani R (2020) Targeting the endothelial Ca2+ toolkit to rescue endothelial dysfunction in obesity associated-hypertension. Curr Med Chem 27:240–257 [DOI] [PubMed] [Google Scholar]

[CR192] 192.Moreno JJ (2017) Eicosanoid receptors: Targets for the treatment of disrupted intestinal epithelial homeostasis. Eur J Pharmacol 796:7–19. 10.1016/j.ejphar.2016.12.004 [DOI] [PubMed] [Google Scholar]

[CR193] 193.Morrow JD (2006) The isoprostanes - unique products of arachidonate peroxidation: their role as mediators of oxidant stress. Curr Pharm Des 12:895–902. 10.2174/138161206776055985 [DOI] [PubMed] [Google Scholar]

[CR194] 194.Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ 2nd (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A 87:9383–9387. 10.1073/pnas.87.23.9383 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR195] 195.Mountian II, Baba-Aïssa F, Jonas JC, De Humbert S, Wuytack F, Parys JB (2001) Expression of Ca(2+) transport genes in platelets and endothelial cells in hypertension. Hypertension 37:135–141. 10.1161/01.hyp.37.1.135 [DOI] [PubMed] [Google Scholar]

[CR196] 196.Nagai H, Kuwahira I, Schwenke DO, Tsuchimochi H, Nara A, Ogura S, Sonobe T, Inagaki T, Fujii Y, Yamaguchi R, Wingenfeld L, Umetani K, Shimosawa T, Yoshida K, Uemura K, Pearson JT, Shirai M (2015) Pulmonary macrophages attenuate hypoxic pulmonary vasoconstriction via β3AR/iNOS pathway in rats exposed to chronic intermittent hypoxia. PLoS One 10:e0131923. 10.1371/journal.pone.0131923 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR197] 197.Nalli AD, Kumar DP, Al-Shboul O, Mahavadi S, Kuemmerle JF, Grider JR, Murthy KS (2014) Regulation of Gβγi-dependent PLC-β3 activity in smooth muscle: inhibitory phosphorylation of PLC-β3 by PKA and PKG and stimulatory phosphorylation of Gαi-GTPase-activating protein RGS2 by PKG. Cell Biochem Biophys 70:867–880. 10.1007/s12013-014-9992-6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR198] 198.Narumiya S, Thumkeo D (2018) Rho signaling research: history, current status and future directions. FEBS Lett 592:1763–1776. 10.1002/1873-3468.13087 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR199] 199.Negri S, Faris P, Moccia F (2021) Reactive oxygen species and endothelial Ca(2+) signaling: Brothers in arms or partners in crime? Int J Mol Sci 22. 10.3390/ijms22189821 [DOI] [PMC free article] [PubMed]

[CR200] 200.Neylon CB, Richards SM, Larsen MA, Agrotis A, Bobik A (1995) Multiple types of ryanodine receptor/Ca2+ release channels are expressed in vascular smooth muscle. Biochem Biophys Res Commun 215:814–821. 10.1006/bbrc.1995.2536 [DOI] [PubMed] [Google Scholar]

[CR201] 201.Novokhatska T, Tishkin S, Dosenko V, Boldyriev A, Ivanova I, Strielkov I, Soloviev A (2013) Correction of vascular hypercontractility in spontaneously hypertensive rats using shRNAs-induced delta protein kinase C gene silencing. Eur J Pharmacol 718:401–407. 10.1016/j.ejphar.2013.08.003 [DOI] [PubMed] [Google Scholar]

[CR202] 202.Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K (2000) Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem 275:3577–3582. 10.1074/jbc.275.5.3577 [DOI] [PubMed] [Google Scholar]

[CR203] 203.Ohta S, Nishihara J, Oka Y, Todo H, Kumon Y, Sakaki S (1995) Possible mechanism to induce protein kinase C-dependent arterial smooth muscle contraction after subarachnoid haemorrhage. Acta Neurochir (Wien) 137:217–225. 10.1007/bf02187196 [DOI] [PubMed] [Google Scholar]

[CR204] 204.Palacios J, Marusic ET, Lopez NC, Gonzalez M, Michea L (2004) Estradiol-induced expression of N(+)-K(+)-ATPase catalytic isoforms in rat arteries: gender differences in activity mediated by nitric oxide donors. Am J Physiol Heart Circ Physiol 286:H1793-1800. 10.1152/ajpheart.00990.2003 [DOI] [PubMed] [Google Scholar]

[CR205] 205.Paneni F, Diaz Cañestro C, Libby P, Lüscher Thomas F, Camici Giovanni G (2017) The aging cardiovascular system. JACC 69:1952–1967. 10.1016/j.jacc.2017.01.064 [DOI] [PubMed] [Google Scholar]

[CR206] 206.Partovian C, Zhuang Z, Moodie K, Lin M, Ouchi N, Sessa WC, Walsh K, Simons M (2005) PKCalpha activates eNOS and increases arterial blood flow in vivo. Circ Res 97:482–487. 10.1161/01.Res.0000179775.04114.45 [DOI] [PubMed] [Google Scholar]

[CR207] 207.Patrignani P (2003) Aspirin insensitive eicosanoid biosynthesis in cardiovascular disease. Thromb Res 110:281–286. 10.1016/s0049-3848(03)00382-7 [DOI] [PubMed] [Google Scholar]

[CR208] 208.Paudyal V, Thapa R, Basnet S, Sharma M, Surani S, Varon J (2025) Updates on pulmonary hypertension. Open Respir Med J 19:e18743064344024. 10.2174/0118743064344024250203101417 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR209] 209.Perez-Gutierrez L, Li P, Ferrara N (2024) Endothelial cell diversity: the many facets of the crystal. Febs J 291:3287–3302. 10.1111/febs.16660 [DOI] [PubMed] [Google Scholar]

[CR210] 210.Phan TX, Ton HT, Gulyás H, Pórszász R, Tóth A, Russo R, Kay MW, Sahibzada N, Ahern GP (2022) TRPV1 in arteries enables a rapid myogenic tone. J Physiol 600:1651–1666. 10.1113/jp281873 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR211] 211.Pires PW, Ko EA, Pritchard HAT, Rudokas M, Yamasaki E, Earley S (2017) The angiotensin II receptor type 1b is the primary sensor of intraluminal pressure in cerebral artery smooth muscle cells. J Physiol 595:4735–4753. 10.1113/jp274310 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR212] 212.Potier M, Gonzalez JC, Motiani RK, Abdullaev IF, Bisaillon JM, Singer HA, Trebak M (2009) Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration. Faseb j 23:2425–2437. 10.1096/fj.09-131128 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR213] 213.Potier M, Gonzalez JC, Motiani RK, Abdullaev IF, Bisaillon JM, Singer HA, Trebak M (2009) Evidence for STIM1- and Orail-dependent storeoperated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration. FASEB J 23:2425–2437. 10.1096/fj.09-131128 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR214] 214.Prakriya M, Lewis RS (2015) Store-operated calcium channels. Physiol Rev 95:1383–1436. 10.1152/physrev.00020.2014 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR215] 215.Pratt PF, Falck JR, Reddy KM, Kurian JB, Campbell WB (1998) 20-HETE relaxes bovine coronary arteries through the release of prostacyclin. Hypertension 31:237–241. 10.1161/01.hyp.31.1.237 [DOI] [PubMed] [Google Scholar]

[CR216] 216.Pronk MCA, van Bezu JSM, van Nieuw Amerongen GP, van Hinsbergh VWM, Hordijk PL (2019) RhoA, RhoB and RhoC differentially regulate endothelial barrier function. Small GTPases 10:466–484. 10.1080/21541248.2017.1339767 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR217] 217.Qiao J, Huang F, Lum H (2003) PKA inhibits RhoA activation: a protection mechanism against endothelial barrier dysfunction. Am J Physiol Lung Cell Mol Physiol 284:L972-980. 10.1152/ajplung.00429.2002 [DOI] [PubMed] [Google Scholar]

[CR218] 218.Qin X, Gao A, Hou X, Xu X, Chen L, Sun L, Hao Y, Shi Y (2022) Connexins may play a critical role in cigarette smoke-induced pulmonary hypertension. Arch Toxicol 96:1609–1621. 10.1007/s00204-022-03274-6 [DOI] [PubMed] [Google Scholar]

[CR219] 219.Radeva MY, Waschke J (2018) Mind the gap: mechanisms regulating the endothelial barrier. Acta Physiol (Oxf) 222. 10.1111/apha.12860 [DOI] [PubMed]

[CR220] 220.Rakugi H, Tabuchi Y, Nakamaru M, Nagano M, Higashimori K, Mikami H, Ogihara T, Suzuki N (1990) Evidence for endothelin-1 release from resistance vessels of rats in response to hypoxia. Biochem Biophys Res Commun 169:973–977. 10.1016/0006-291x(90)91989-6 [DOI] [PubMed] [Google Scholar]

[CR221] 221.Randriamboavonjy V, Busse R, Fleming I (2003) 20-HETE-induced contraction of small coronary arteries depends on the activation of Rho-kinase. Hypertension 41:801–806. 10.1161/01.Hyp.0000047240.33861.6b [DOI] [PubMed] [Google Scholar]

[CR222] 222.Raturi A, Simmen T (2013) Where the endoplasmic reticulum and the mitochondrion tie the knot: the mitochondria-associated membrane (MAM). Biochim Biophys Acta 1833:213–224. 10.1016/j.bbamcr.2012.04.013 [DOI] [PubMed] [Google Scholar]

[CR223] 223.Ray A, Ch. Maharana K, Meenakshi S, Singh S (2023) Endothelial dysfunction and its relation in different disorders: Recent update. Health Sci Rev 7:100084. 10.1016/j.hsr.2023.100084 [Google Scholar]

[CR224] 224.Renaud JM, Gramolini A, Light P, Comtois A (1996) Modulation of muscle contractility during fatigue and recovery by ATP sensitive potassium channel. Acta Physiol Scand 156:203–212. 10.1046/j.1365-201X.1996.210000.x [DOI] [PubMed] [Google Scholar]

[CR225] 225.Ringvold HC, Khalil RA (2017) Protein kinase C as regulator of vascular smooth muscle function and potential target in vascular disorders. Adv Pharmacol 78:203–301. 10.1016/bs.apha.2016.06.002 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR226] 226.Rinne A, Banach K, Blatter LA (2009) Regulation of nuclear factor of activated T cells (NFAT) in vascular endothelial cells. J Mol Cell Cardiol 47:400–410. 10.1016/j.yjmcc.2009.06.010 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR227] 227.Roberts LJ 2nd, Milne GL (2009) Isoprostanes. J Lipid Res 50(Suppl):S219-223. 10.1194/jlr.R800037-JLR200 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR228] 228.Rodrigo GC, Standen NB (2005) ATP-sensitive potassium channels. Curr Pharm Des 11:1915–1940. 10.2174/1381612054021015 [DOI] [PubMed] [Google Scholar]

[CR229] 229.Roman RJ, Renic M, Dunn KM, Takeuchi K, Hacein-Bey L (2006) Evidence that 20-HETE contributes to the development of acute and delayed cerebral vasospasm. Neurol Res 28:738–749. 10.1179/016164106x152016 [DOI] [PubMed] [Google Scholar]

[CR230] 230.Ron D, Kazanietz MG (1999) New insights into the regulation of protein kinase C and novel phorbol ester receptors. Faseb j 13:1658–1676 [PubMed] [Google Scholar]

[CR231] 231.Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Veliçelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169:435–445. 10.1083/jcb.200502019 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR232] 232.Roshanravan H, Kim EY, Dryer SE (2016) 20-Hydroxyeicosatetraenoic acid (20-HETE) modulates canonical transient receptor potential-6 (TRPC6) channels in podocytes. Front Physiol 7:351. 10.3389/fphys.2016.00351 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR233] 233.Rovetti R, Cui X, Garfinkel A, Weiss JN, Qu Z (2010) Spark-induced sparks as a mechanism of intracellular calcium alternans in cardiac myocytes. Circ Res 106:1582–1591. 10.1161/circresaha.109.213975 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR234] 234.Saida K, Van Breemen C (1984) Cyclic AMP modulation of adrenoreceptor-mediated arterial smooth muscle contraction. J Gen Physiol 84:307–318. 10.1085/jgp.84.2.307 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR235] 235.Saint-Martin Willer A, Montani D, Capuano V, Antigny F (2024) Orai1/STIMs modulators in pulmonary vascular diseases. Cell Calcium 121:102892. 10.1016/j.ceca.2024.102892 [DOI] [PubMed] [Google Scholar]

[CR236] 236.Salamanca DA, Khalil RA (2005) Protein kinase C isoforms as specific targets for modulation of vascular smooth muscle function in hypertension. Biochem Pharmacol 70:1537–1547. 10.1016/j.bcp.2005.07.017 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR237] 237.Saleh S, Albert A, Peppiatt-Wildman C, Large W (2007) Angiotensin II activates two cation conductances with distinct TRPC1 and TRPC6 channel properties in rabbit mesenteric artery myocytes. J Physiol 577:479–495. 10.1113/jphysiol.2006.119305 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR238] 238.Sandoval YH, Atef ME, Levesque LO, Li Y, Anand-Srivastava MB (2014) Endothelin-1 signaling in vascular physiology and pathophysiology. Curr Vasc Pharmacol 12:202–214. 10.2174/1570161112666140226122054 [DOI] [PubMed] [Google Scholar]

[CR239] 239.Santulli G, Nakashima R, Yuan Q, Marks AR (2017) Intracellular calcium release channels: an update. J Physiol 595:3041–3051. 10.1113/jp272781 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR240] 240.Shan J, Resnick LM, Liu QY, Wu XC, Barbagallo M, Pang PK (1994) Vascular effects of 17 beta-estradiol in male Sprague-Dawley rats. Am J Physiol 266:H967-973. 10.1152/ajpheart.1994.266.3.H967 [DOI] [PubMed] [Google Scholar]

[CR241] 241.Sharif-Naeini R, Folgering JH, Bichet D, Duprat F, Lauritzen I, Arhatte M, Jodar M, Dedman A, Chatelain FC, Schulte U, Retailleau K, Loufrani L, Patel A, Sachs F, Delmas P, Peters DJ, Honoré E (2009) Polycystin-1 and -2 dosage regulates pressure sensing. Cell 139:587–596. 10.1016/j.cell.2009.08.045 [DOI] [PubMed] [Google Scholar]

[CR242] 242.Shi J, Mori E, Mori Y, Mori M, Li J, Ito Y, Inoue R (2004) Multiple regulation by calcium of murine homologues of transient receptor potential proteins TRPC6 and TRPC7 expressed in HEK293 cells. J Physiol 561:415–432. 10.1113/jphysiol.2004.075051 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR243] 243.Shi W-W, Yang Y, Shi Y, Jiang C (2012) K(ATP) channel action in vascular tone regulation: from genetics to diseases. Sheng Li Xue Bao 64:1–13 [PMC free article] [PubMed] [Google Scholar]

[CR244] 244.Shi Y, Vanhoutte PM (2008) Oxidative stress and COX cause hyper-responsiveness in vascular smooth muscle of the femoral artery from diabetic rats. Br J Pharmacol 154:639–651. 10.1038/bjp.2008.110 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR245] 245.Shimokawa H, Sunamura S, Satoh K (2016) RhoA/Rho-Kinase in the cardiovascular system. Circ Res 118:352–366. 10.1161/circresaha.115.306532 [DOI] [PubMed] [Google Scholar]

[CR246] 246.Shin WS, Berkowitz DE, Ryoo SW (2012) Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice. Exp Mol Med 44:594–602. 10.3858/emm.2012.44.10.068 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR247] 247.Schildknecht S, Ullrich V (2009) Peroxynitrite as regulator of vascular prostanoid synthesis. Arch Biochem Biophys 484:183–189. 10.1016/j.abb.2008.10.023 [DOI] [PubMed] [Google Scholar]

[CR248] 248.Schleifenbaum J, Kassmann M, Szijártó IA, Hercule HC, Tano JY, Weinert S, Heidenreich M, Pathan AR, Anistan YM, Alenina N, Rusch NJ, Bader M, Jentsch TJ, Gollasch M (2014) Stretch-activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries. Circ Res 115:263–272. 10.1161/circresaha.115.302882 [DOI] [PubMed] [Google Scholar]

[CR249] 249.Schmidt K, Dubrovska G, Nielsen G, Fesüs G, Uhrenholt TR, Hansen PB, Gudermann T, Dietrich A, Gollasch M, de Wit C, Köhler R (2010) Amplification of EDHF-type vasodilatations in TRPC1-deficient mice. Br J Pharmacol 161:1722–1733. 10.1111/j.1476-5381.2010.00985.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR250] 250.Schofield I, Malik R, Izzard A, Austin C, Heagerty A (2002) Vascular structural and functional changes in type 2 diabetes mellitus: evidence for the roles of abnormal myogenic responsiveness and dyslipidemia. Circulation 106:3037–3043. 10.1161/01.cir.0000041432.80615.a5 [DOI] [PubMed] [Google Scholar]

[CR251] 251.Singh SS, Chauhan A, Brockerhoff H, Chauhan VP (1993) Activation of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. Biochem Biophys Res Commun 195:104–112. 10.1006/bbrc.1993.2016 [DOI] [PubMed] [Google Scholar]

[CR252] 252.Slish DF, Welsh DG, Brayden JE (2002) Diacylglycerol and protein kinase C activate cation channels involved in myogenic tone. Am J Physiol Heart Circ Physiol 283:H2196-2201. 10.1152/ajpheart.00605.2002 [DOI] [PubMed] [Google Scholar]

[CR253] 253.Soma S, Kuwashima H, Matsumura C, Kimura T (2009) Involvement of protein kinase C in the regulation of Na+/Ca2+ exchanger in bovine adrenal chromaffin cells. Clin Exp Pharmacol Physiol 36:717–723. 10.1111/j.1440-1681.2009.05140.x [DOI] [PubMed] [Google Scholar]

[CR254] 254.Somlyo AV, Bond M, Somlyo AP, Scarpa A (1985) Inositol trisphosphate-induced calcium release and contraction in vascular smooth muscle. Proc Natl Acad Sci U S A 82:5231–5235. 10.1073/pnas.82.15.5231 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR255] 255.Song T, Hao Q, Zheng YM, Liu QH, Wang YX (2015) Inositol 1,4,5-trisphosphate activates TRPC3 channels to cause extracellular Ca2+ influx in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 309:L1455-1466. 10.1152/ajplung.00148.2015 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR256] 256.Song X, Liu Y, Dong L, Wang Y (2018) Stromal-interacting molecule 1 (Stim1)/Orai1 modulates endothelial permeability in ventilator-induced lung injury. Med Sci Monit 24:9413–9423. 10.12659/msm.911268 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR257] 257.Steinberg SF (2008) Structural basis of protein kinase C isoform function. Physiol Rev 88:1341–1378. 10.1152/physrev.00034.2007 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR258] 258.Sumi T, Matsumoto K, Nakamura T (2001) Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase. J Biol Chem 276:670–676. 10.1074/jbc.M007074200 [DOI] [PubMed] [Google Scholar]

[CR259] 259.Suzuki Y (2025) Ca2+ microdomains in vascular smooth muscle cells: Roles in vascular tone regulation and hypertension. J Pharmacol Sci 158:59–67. 10.1016/j.jphs.2025.03.008 [DOI] [PubMed] [Google Scholar]

[CR260] 260.Swain SM, Romac JM, Shahid RA, Pandol SJ, Liedtke W, Vigna SR, Liddle RA (2020) TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation. J Clin Invest 130:2527–2541. 10.1172/jci134111 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR261] 261.Taguchi K, Kaneko K, Kubo T (2000) Protein kinase C modulates Ca2+-activated K+ channels in cultured rat mesenteric artery smooth muscle cells. Biol Pharm Bull 23:1450–1454. 10.1248/bpb.23.1450 [DOI] [PubMed] [Google Scholar]

[CR262] 262.Tang EH, Leung FP, Huang Y, Feletou M, So KF, Man RY, Vanhoutte PM (2007) Calcium and reactive oxygen species increase in endothelial cells in response to releasers of endothelium-derived contracting factor. Br J Pharmacol 151:15–23. 10.1038/sj.bjp.0707190 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR263] 263.Tano JY, Schleifenbaum J, Gollasch M (2014) Perivascular adipose tissue, potassium channels, and vascular dysfunction. Arterioscler Thromb Vasc Biol 34:1827–1830. 10.1161/atvbaha.114.303032 [DOI] [PubMed] [Google Scholar]

[CR264] 264.Thillaiappan NB, Chakraborty P, Hasan G, Taylor CW (2019) IP(3) receptors and Ca(2+) entry. Biochim Biophys Acta Mol Cell Res 1866:1092–1100. 10.1016/j.bbamcr.2018.11.007 [DOI] [PubMed] [Google Scholar]

[CR265] 265.Thompson J, Khalil RA (2003) Gender differences in the regulation of vascular tone. Clin Exp Pharmacol Physiol 30:1–15. 10.1046/j.1440-1681.2003.03790.x [DOI] [PubMed] [Google Scholar]

[CR266] 266.Thorin E, Clozel M (2010) The cardiovascular physiology and pharmacology of endothelin-1. Adv Pharmacol 60:1–26. 10.1016/b978-0-12-385061-4.00001-5 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR267] 267.Thorin E, Webb DJ (2010) Endothelium-derived endothelin-1. Pflugers Arch 459:951–958. 10.1007/s00424-009-0763-y [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR268] 268.Tian XY, Wong WT, Leung FP, Zhang Y, Wang YX, Lee HK, Ng CF, Chen ZY, Yao X, Au CL, Lau CW, Vanhoutte PM, Cooke JP, Huang Y (2012) Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin f(2α) impairs endothelial function in renovascular hypertensive rats. Antioxid Redox Signal 16:363–373. 10.1089/ars.2010.3874 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR269] 269.Topper JN, Cai J, Falb D, Gimbrone MA Jr (1996) Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A 93:10417–10422. 10.1073/pnas.93.19.10417 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR270] 270.Toussaint F, Charbel C, Allen BG, Ledoux J (2016) Vascular CaMKII: heart and brain in your arteries. Am J Physiol Cell Physiol 311:C462–C478. 10.1152/ajpcell.00341.2015 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR271] 271.Touyz RM, Alves-Lopes R, Rios FJ, Camargo LL, Anagnostopoulou A, Arner A, Montezano AC (2018) Vascular smooth muscle contraction in hypertension. Cardiovasc Res 114:529–539. 10.1093/cvr/cvy023 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR272] 272.Tran QK, Firkins R, Giles J, Francis S, Matnishian V, Tran P, VerMeer M, Jasurda J, Burgard MA, Gebert-Oberle B (2016) Estrogen enhances linkage in the vascular endothelial calmodulin network via a feedforward mechanism at the g protein-coupled estrogen receptor 1. J Biol Chem 291:10805–10823. 10.1074/jbc.M115.697334 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR273] 273.Treiber FA, Kamarck T, Schneiderman N, Sheffield D, Kapuku G, Taylor T (2003) Cardiovascular reactivity and development of preclinical and clinical disease states. Psychosom Med 65:46–62. 10.1097/00006842-200301000-00007 [DOI] [PubMed] [Google Scholar]

[CR274] 274.Tsang SY, Yao X, Wong CM, Chan FL, Chen ZY, Huang Y (2004) Differential regulation of K+ and Ca2+ channel gene expression by chronic treatment with estrogen and tamoxifen in rat aorta. Eur J Pharmacol 483:155–162. 10.1016/j.ejphar.2003.10.031 [DOI] [PubMed] [Google Scholar]

[CR275] 275.Tu H, Wang Z, Bezprozvanny I (2005) Modulation of mammalian inositol 1,4,5-trisphosphate receptor isoforms by calcium: a role of calcium sensor region. Biophys J 88:1056–1069. 10.1529/biophysj.104.049601 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR276] 276.Tykocki NR, Boerman EM, Jackson WF (2017) Smooth muscle ion channels and regulation of vascular tone in resistance arteries and arterioles. Compr Physiol 7:485–581. 10.1002/cphy.c160011 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR277] 277.Ullrich ND, Koschak A, MacLeod KT (2007) Oestrogen directly inhibits the cardiovascular L-type Ca2+ channel Cav1.2. Biochem Biophys Res Commun 361:522–527. 10.1016/j.bbrc.2007.07.054 [DOI] [PubMed] [Google Scholar]

[CR278] 278.van Splunder H, Villacampa P, Martínez-Romero A, Graupera M (2024) Pericytes in the disease spotlight. Trends Cell Biol 34:58–71. 10.1016/j.tcb.2023.06.001 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR279] 279.Vangeel L, Voets T (2019) Transient receptor potential channels and calcium signaling. Cold Spring Harb Perspect Biol 11. 10.1101/cshperspect.a035048 [DOI] [PMC free article] [PubMed]

[CR280] 280.Vanhoutte PM, Feletou M, Taddei S (2005) Endothelium-dependent contractions in hypertension. Br J Pharmacol 144:449–458. 10.1038/sj.bjp.0706042 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR281] 281.Vanhoutte PM, Shimokawa H, Feletou M, Tang EH (2017) Endothelial dysfunction and vascular disease - a 30th anniversary update. Acta Physiol (Oxf) 219:22–96. 10.1111/apha.12646 [DOI] [PubMed] [Google Scholar]

[CR282] 282.Vanhoutte PM, Tang EH (2008) Endothelium-dependent contractions: when a good guy turns bad! J Physiol 586:5295–5304. 10.1113/jphysiol.2008.161430 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR283] 283.Várnai P, Hunyady L, Balla T (2009) STIM and Orai: the long-awaited constituents of store-operated calcium entry. Trends Pharmacol Sci 30:118–128. 10.1016/j.tips.2008.11.005 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR284] 284.Virdis A, Bacca A, Colucci R, Duranti E, Fornai M, Materazzi G, Ippolito C, Bernardini N, Blandizzi C, Bernini G, Taddei S (2013) Endothelial dysfunction in small arteries of essential hypertensive patients: role of cyclooxygenase-2 in oxidative stress generation. Hypertension 62:337–344. 10.1161/hypertensionaha.111.00995 [DOI] [PubMed] [Google Scholar]

[CR285] 285.Walker JW, Somlyo AV, Goldman YE, Somlyo AP, Trentham DR (1987) Kinetics of smooth and skeletal muscle activation by laser pulse photolysis of caged inositol 1,4,5-trisphosphate. Nature 327:249–252. 10.1038/327249a0 [DOI] [PubMed] [Google Scholar]

[CR286] 286.Wang D, Wang C, Wu X, Zheng W, Sandberg K, Ji H, Welch WJ, Wilcox CS (2014) Endothelial dysfunction and enhanced contractility in microvessels from ovariectomized rats: roles of oxidative stress and perivascular adipose tissue. Hypertension 63:1063–1069. 10.1161/hypertensionaha.113.02284 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR287] 287.Wang R, Sauvé R, de Champlain J (1995) Abnormal regulation of cytosolic free calcium in vascular endothelial cells from spontaneously hypertensive rats. J Hypertens 13:993–1001 [PubMed] [Google Scholar]

[CR288] 288.Wang Y, Zheng XR, Riddick N, Bryden M, Baur W, Zhang X, Surks HK (2009) ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res 104:531–540. 10.1161/circresaha.108.188524 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR289] 289.Westcott EB, Jackson WF (2011) Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles. Am J Physiol Heart Circ Physiol 300:H1616-1630. 10.1152/ajpheart.00728.2010 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR290] 290.Wilson C, Lee MD, McCarron JG (2016) Acetylcholine released by endothelial cells facilitates flow-mediated dilatation. J Physiol 594:7267–7307. 10.1113/jp272927 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR291] 291.Wilson C, Zhang X, Buckley C, Heathcote HR, Lee MD, McCarron JG (2019) Increased vascular contractility in hypertension results from impaired endothelial calcium signaling. Hypertension 74:1200–1214. 10.1161/hypertensionaha.119.13791 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR292] 292.Wong MS, Delansorne R, Man RY, Vanhoutte PM (2008) Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 295:H289-296. 10.1152/ajpheart.00116.2008 [DOI] [PubMed] [Google Scholar]

[CR293] 293.Wong MS, Vanhoutte PM (2010) COX-mediated endothelium-dependent contractions: from the past to recent discoveries. Acta Pharmacol Sin 31:1095–1102. 10.1038/aps.2010.127 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR294] 294.Wong SL, Leung FP, Lau CW, Au CL, Yung LM, Yao X, Chen ZY, Vanhoutte PM, Gollasch M, Huang Y (2009) Cyclooxygenase-2-derived prostaglandin F2alpha mediates endothelium-dependent contractions in the aortae of hamsters with increased impact during aging. Circ Res 104:228–235. 10.1161/circresaha.108.179770 [DOI] [PubMed] [Google Scholar]

[CR295] 295.Woodsome TP, Eto M, Everett A, Brautigan DL, Kitazawa T (2001) Expression of CPI-17 and myosin phosphatase correlates with Ca(2+) sensitivity of protein kinase C-induced contraction in rabbit smooth muscle. J Physiol 535:553–564. 10.1111/j.1469-7793.2001.t01-1-00553.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR296] 296.Worley PF, Zeng W, Huang GN, Yuan JP, Kim JY, Lee MG, Muallem S (2007) TRPC channels as STIM1-regulated store-operated channels. Cell Calcium 42:205–211. 10.1016/j.ceca.2007.03.004 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR297] 297.Wray S, Smith RD (2004) Mechanisms of action of pH-induced effects on vascular smooth muscle. Mol Cell Biochem 263:163–172. 10.1023/B:MCBI.0000041858.78005.d2 [DOI] [PubMed] [Google Scholar]

[CR298] 298.Wright NT, Prosser BL, Varney KM, Zimmer DB, Schneider MF, Weber DJ (2008) S100A1 and calmodulin compete for the same binding site on ryanodine receptor. J Biol Chem 283:26676–26683. 10.1074/jbc.M804432200 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR299] 299.Wu Y, Fu J, Huang Y, Duan R, Zhang W, Wang C, Wang S, Hu X, Zhao H, Wang L, Liu J, Gao G, Yuan P (2023) Biology and function of pericytes in the vascular microcirculation. Animal Model Exp Med 6:337–345. 10.1002/ame2.12334 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR300] 300.Xu SZ, Boulay G, Flemming R, Beech DJ (2006) E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles. Am J Physiol Heart Circ Physiol 291:H2653-2659. 10.1152/ajpheart.00495.2006 [DOI] [PubMed] [Google Scholar]

[CR301] 301.Yamada M, Lamping KG, Duttaroy A, Zhang W, Cui Y, Bymaster FP, McKinzie DL, Felder CC, Deng CX, Faraci FM, Wess J (2001) Cholinergic dilation of cerebral blood vessels is abolished in M(5) muscarinic acetylcholine receptor knockout mice. Proc Natl Acad Sci U S A 98:14096–14101. 10.1073/pnas.251542998 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR302] 302.Yamaguchi H, Igarashi M, Hirata A, Sugae N, Tsuchiya H, Jimbu Y, Tominaga M, Kato T (2004) Altered PDGF-BB-induced p38 MAP kinase activation in diabetic vascular smooth muscle cells: roles of protein kinase C-delta. Arterioscler Thromb Vasc Biol 24:2095–2101. 10.1161/01.Atv.0000144009.35400.65 [DOI] [PubMed] [Google Scholar]

[CR303] 303.Yamaguchi Y, Katoh H, Yasui H, Aoki J, Nakamura K, Negishi M (2000) Galpha(12) and galpha(13) inhibit Ca(2+)-dependent exocytosis through Rho/Rho-associated kinase-dependent pathway. J Neurochem 75:708–717. 10.1046/j.1471-4159.2000.0750708.x [DOI] [PubMed] [Google Scholar]

[CR304] 304.Yamamoto H, van Breemen C (1985) Inositol-1,4,5-trisphosphate releases calcium from skinned cultured smooth muscle cells. Biochem Biophys Res Commun 130:270–274. 10.1016/0006-291x(85)90412-7 [DOI] [PubMed] [Google Scholar]

[CR305] 305.Yang D, Félétou M, Levens N, Zhang JN, Vanhoutte PM (2003) A diffusible substance(s) mediates endothelium-dependent contractions in the aorta of SHR. Hypertension 41:143–148. 10.1161/01.hyp.0000047651.45322.16 [DOI] [PubMed] [Google Scholar]

[CR306] 306.Yang Z, Ming XF (2013) Arginase: the emerging therapeutic target for vascular oxidative stress and inflammation. Front Immunol 4:149. 10.3389/fimmu.2013.00149 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR307] 307.Yao L, Romero MJ, Toque HA, Yang G, Caldwell RB, Caldwell RW (2010) The role of RhoA/Rho kinase pathway in endothelial dysfunction. J Cardiovasc Dis Res 1:165–170. 10.4103/0975-3583.74258 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR308] 308.Yeh HI, Chang HM, Lu WW, Lee YN, Ko YS, Severs NJ, Tsai CH (2000) Age-related alteration of gap junction distribution and connexin expression in rat aortic endothelium. J Histochem Cytochem 48:1377–1389. 10.1177/002215540004801008 [DOI] [PubMed] [Google Scholar]

[CR309] 309.Yiu SS, Zhao X, Inscho EW, Imig JD (2003) 12-Hydroxyeicosatetraenoic acid participates in angiotensin II afferent arteriolar vasoconstriction by activating L-type calcium channels. J Lipid Res 44:2391–2399. 10.1194/jlr.M300183-JLR200 [DOI] [PubMed] [Google Scholar]

[CR310] 310.Yu M, McAndrew RP, Al-Saghir R, Maier KG, Medhora M, Roman RJ (1985) Jacobs ER (2002) Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries. J Appl Physiol 93:1391–1399. 10.1152/japplphysiol.00247.2002 [DOI] [PubMed] [Google Scholar]

[CR311] 311.Yu X, Ma H, Barman SA, Liu AT, Sellers M, Stallone JN, Prossnitz ER, White RE, Han G (2011) Activation of G protein-coupled estrogen receptor induces endothelium-independent relaxation of coronary artery smooth muscle. Am J Physiol Endocrinol Metab 301:E882-888. 10.1152/ajpendo.00037.2011 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR312] 312.Zeng Q, Han Y, Bao Y, Li W, Li X, Shen X, Wang X, Yao F, O’Rourke ST, Sun C (2010) 20-HETE increases NADPH oxidase-derived ROS production and stimulates the L-type Ca2+ channel via a PKC-dependent mechanism in cardiomyocytes. Am J Physiol Heart Circ Physiol 299:H1109-1117. 10.1152/ajpheart.00067.2010 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR313] 313.Zhai H, Liu H, Shang B, Zou X (2023) Sarsasapogenin blocks ox-LDL-stimulated vascular smooth muscle cell proliferation, migration, and invasion through suppressing STIM1 expression. Cardiovasc Diagn Ther 13:441–452. 10.21037/cdt-23-111 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR314] 314.Zhang F, Ram JL, Standley PR, Sowers JR (1994) 17 beta-Estradiol attenuates voltage-dependent Ca2+ currents in A7r5 vascular smooth muscle cell line. Am J Physiol 266:C975-980. 10.1152/ajpcell.1994.266.4.C975 [DOI] [PubMed] [Google Scholar]

[CR315] 315.Zhao T, Parmisano S, Soroureddin Z, Zhao M, Yung L, Thistlethwaite PA, Makino A, Yuan JX (2022) Mechanosensitive cation currents through TRPC6 and Piezo1 channels in human pulmonary arterial endothelial cells. Am J Physiol Cell Physiol 323:C959-c973. 10.1152/ajpcell.00313.2022 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR316] 316.Zheng J (2013) Molecular mechanism of TRP channels. Compr Physiol 3:221–242. 10.1002/cphy.c120001 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR317] 317.Zhou N, Lee JJ, Stoll S, Ma B, Costa KD, Qiu H (2017) Rho kinase regulates aortic vascular smooth muscle cell stiffness via Actin/SRF/Myocardin in hypertension. Cell Physiol Biochem 44:701–715. 10.1159/000485284 [DOI] [PMC free article] [PubMed] [Google Scholar]

[CR318] 318.Zhu MX, Tang J (2004) TRPC channel interactions with calmodulin and IP3 receptors. Novartis Found Symp 258:44–58 discussion 58-62, 98-102, 263-106 [PubMed] [Google Scholar]

[CR319] 319.Zou AP, Fleming JT, Falck JR, Jacobs ER, Gebremedhin D, Harder DR, Roman RJ (1996) 20-HETE is an endogenous inhibitor of the large-conductance Ca(2+)-activated K+ channel in renal arterioles. Am J Physiol 270:R228-237. 10.1152/ajpregu.1996.270.1.R228 [DOI] [PubMed] [Google Scholar]

[CR320] 320.Zou Y, Akazawa H, Qin Y, Sano M, Takano H, Minamino T, Makita N, Iwanaga K, Zhu W, Kudoh S, Toko H, Tamura K, Kihara M, Nagai T, Fukamizu A, Umemura S, Iiri T, Fujita T, Komuro I (2004) Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol 6:499–506. 10.1038/ncb1137 [DOI] [PubMed] [Google Scholar]

PERMALINK

The machinery of healthy vasoconstriction: an overview

Jana Pourová

Patrícia Dias

Milan Pour

Přemysl Mladěnka

Abstract

Introduction

Vascular smooth muscle in vasoconstriction

Calcium ions

Intracellular Ca2+ sources

Extracellular Ca2+ sources

SOCE

Effects of Ca2+

The Ca2+ feedback

Fig. 1.

Protein kinase C

Activation of PKC

Effects of activated PKC

The PKC feedback

Fig. 2.

Fig. 3.

RhoA/ROCK system

Activation of RhoA and ROCK

ROCK and its effects

The RhoA/ROCK feedback

Fig. 4.

Endothelium in vasoconstriction

Endothelium-derived contracting factors EDCFs

Endothelin 1

Prostanoids causing vasoconstriction

Hydroxyeicosatetraenoic acids

Other pro-vasoconstrictive factors

Endothelial vasoconstriction counteracting previous stimuli

Fig. 5.

Vasoconstrictive stimuli

Mechanical stimuli

Thermal stimuli

Chemical stimuli

Conclusions

Author contribution

Funding

Data availability

Declarations

Ethical approval and Consent to participate

Human ethics

Consent for publication

Clinical trial number

Competing interests

Footnotes

References

Associated Data

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases

Intracellular Ca²⁺ sources

Extracellular Ca²⁺ sources

Effects of Ca²⁺

The Ca²⁺ feedback