FIG. 6.
Mechanisms of vascular tone regulation by H2S. H2S may dilate blood vessels by activating different types of potassium channels, that is, ATP-inhibited (KATP), inwardly rectifying (Kir), voltage-sensitive (Kv), KCNQ, and large conductance Ca2+-activated (BKCa). By suppressing cytochrome c oxidase, H2S may inhibit ATP synthesis leading to the de-repression of KATP channels. Vasodilation may also be mediated by activation of HCO3− efflux through the HCO3−/Cl− exchanger, inhibition of cGMP-degrading phosphodiesterase (PDE), angiotensin-converting enzyme (ACE), and NADPH oxidase (NOX)—the source of nitric oxide (NO) scavenger, superoxide (O2−•). Finally, by stimulating endothelial cell small- and intermediate-conductance Ca2+-activated potassium channels (SKCa and IKCa), H2S may trigger endothelium-dependent hyperpolarization. On the other hand, H2S may constrict blood vessels by inhibiting adenylate cyclase, scavenging NO to form nitrosothiol, inhibiting l-arginine (l-Arg) transport to endothelial cells and eNOS activity, as well as by stimulating efflux of superoxide, which then binds NO to form peroxynitrite (ONOO−) in the extracellular space. Effects of H2S resulting in vasodilation and vasoconstriction are shown in green and red, respectively. (To see this illustration in color the reader is referred to the web version of this article at www.liebertonline.com/ars). sGC, soluble guanylyl cyclase; eNOS, endothelial nitric oxide synthase.