Hydrogen Sulfide and Endothelium-Dependent Vasorelaxation

In addition to nitric oxide and carbon monoxide, hydrogen sulfide (H(2)S), synthesized enzymatically from l-cysteine or l-homocysteine, is the third gasotransmitter in mammals. Endogenous H(2)S is involved in the regulation of many physiological processes, including vascular tone. Although initially it was suggested that in the vascular wall H(2)S is synthesized only by smooth muscle cells and relaxes them by activating ATP-sensitive potassium channels, more recent studies indicate that H(2)S is synthesized in endothelial cells as well. Endothelial H(2)S production is stimulated by many factors, including acetylcholine, shear stress, adipose tissue hormone leptin, estrogens and plant flavonoids. In some vascular preparations H(2)S plays a role of endothelium-derived hyperpolarizing factor by activating small and intermediate-conductance calcium-activated potassium channels. Endothelial H(2)S signaling is up-regulated in some pathologies, such as obesity and cerebral ischemia-reperfusion. In addition, H(2)S activates endothelial NO synthase and inhibits cGMP degradation by phosphodiesterase 5 thus potentiating the effect of NO-cGMP pathway. Moreover, H(2)S-derived polysulfides directly activate protein kinase G. Finally, H(2)S interacts with NO to form nitroxyl (HNO)—a potent vasorelaxant. H(2)S appears to play an important and multidimensional role in endothelium-dependent vasorelaxation.