Figure 5.

Regulatory effect of NO, H₂S, and S-nitrosothiols on vascular tone. Depending upon the concentration, H₂S exerts biphasic response on vascular tone. At high concentration (NaHS > 100 μM), H₂S acts as a potent vasodilator by opening of K_ATP and K_V channels, downregulating ATP levels and cellular metabolism, regulating intracellular pH and release of endothelium-derived hyperpolarizing factor (EDHF). At low concentration (NaHS < 100 μM), however, H₂S acts as a vasoconstrictor by inhibiting eNOS-derived NO production and intracellular cAMP pathway. NO, by itself, is a strong vasodilator. Acting via cGMP-PKG pathway, it stimulates opening of K_ATP and ATP-sensitive potassium channels. It also increases Ca²⁺ reuptake by endoplasmic reticulum and thus decreases intracellular Ca²⁺ levels resulting in less contraction. NO signaling is also stimulated by high concentration of H₂S, contributing to its vasodilatory effect. S-nitrothiols, derived from interplay between NO and H₂S, act as vasodilators mainly via NO signaling.