Table 2.

Summary of endothelial TRPV4 channel-dependent vasodilatory mechanisms in different vascular beds.

Vascular bed	Species	Endothelial TRPV4 channel-dependent mechanism	References
Cerebral arteries	Rat, mouse, human	✓ PLA2 activation increases endothelial Ca2+ influx through TRPV4 channels ✓ acetylcholine-dependent vasodilation via TRPV4 channels ✓ GqPCR signaling activates endothelial TRPV4 channels over Kir2.1 channels	Harraz et al. (2018), Hatano, Suzuki, Itoh, and Muraki (2013), Marrelli et al. (2007), Zhang et al. (2013)
Retinal artery	Bovine	✓ TRPV4 channel control intracellular Ca2+ concentration in cultured retinal microvascular ECs	Monaghan et al. (2015)
Carotid artery	Rat, mouse	✓ TRPV4 channel activation triggers NO- and EDH-dependent vasodilation ✓ Dynamic TRPV4/SK channel complexes in caveolae of ECs promote flow-mediated vasodilation ✓ Flow-induced endothelium-dependent vasodilation via activation of cytochrome P450 epoxygenase-EETs-TRPV4 channel signaling	Goedicke-Fritz et al. (2015), Kohler et al. (2006), Loot et al. (2008)
Arteria gracilis	Rat	✓ TRPV4 channel activation triggers NO- and EDH-dependent vasodilation ✓ Acetylcholine activates TRPV4 channel-mediated Ca2+ signals ✓ TRPV4-SK/IK channel signaling ✓ Co-localization of Cav-1, TRPV4, and BK channels promotes vasodilation	Kohler et al. (2006), Naik and Walker (2018)
Microvascular ECs	Human	✓ Caveolar association of Cav-1, TRPV4 and SK channels in microvascular ECs ✓ Shear stress induces a partial de novo colocalization of IK channels with Cav-1 and TRPV4 channels ✓ PUFAs enhance TRPV4 channel activity by modifying cell membrane fluidity and bending stiffness	Caires et al. (2017), Goedicke-Fritz et al. (2015)
Feed artery	Human	✓ TRPV4 channels attenuate α1-adrenergic vasoconstriction	Gifford et al. (2014)
Coronary artery	Human	✓ Flow-induced activation of endothelial TRPV4 channels and mitochondrial reactive oxygen species production ✓ Arachidonic acid-activation of TRPV4 channels via PKA-mediated phosphorylation	Bubolz et al. (2012), Cao et al. (2018), Zheng et al. (2013)
Pulmonary artery	Rat, mouse	✓ Endothelium-dependent vasodilation mainly through TRPV4-eNOS signaling ✓ NO release activates endothelial GC-PKG-dependent negative-feedback pathway that limits TRPV4 channel activity ✓ ATP dilates pulmonary arteries mainly via TRPV4-eNOS signalings ✓ Endothelial Cav-1-PKC-TRPV4 channel signaling promotes vasodilation	Marziano et al. (2017), Marziano et al. (2019), Sukumaran et al. (2013)
Mesenteric artery	Mouse, rat	✓ EDH-dependent dilation in resistance arteries, EDH- and NO-dependent dilation in conduit arteries ✓ 11,12-EET induces TRPV4 channel activation and vasodilation ✓ Shear stress dilates via NO- and EDH-dependent mechanisms ✓ PKCα-TRPV4 channel signaling mediates vasodilation to acetylcholine ✓ Cooperative TRPV4 channel openings increase endothelial Ca2+ influx and cause vasodilation through IK and SK channels ✓ TRPV4 channels colocalize with Cav-1 ✓ PKC-AKAP150-TRPV4 channel signaling at MEPs underlies vasodilation ✓ Endothelial TRPV4-C1-P2 complex mediates flow-induced Ca2+ entry	Adapala et al. (2011), Du et al. (2014), Earley et al. (2009), Ma et al. (2013), Mendoza et al. (2010), Rath et al. (2012), Seki et al. (2017), Sonkusare et al. (2012)
Uterine radial artery	Rat	✓ The number of endothelial TRPV4 channels and caveolae is increased in pregnancy	Senadheera et al. (2013)
Bladder vessel	Rat, mouse	✓ Endothelial TRPV4 channels are expressed	Gevaert et al. (2007)
Cremaster artery	Rat	✓ Endothelial TRPV4 channels increase Ca2+ signal frequency at MEPs in response to low intraluminal pressure	Bagher et al. (2012)