The Role of Hydrogen Sulfide as an Endogenous Vasorelaxant Factor

Abstract

Hydrogen sulfide (H2S) is a small molecule of gas with important physiological functions. The endogenous production of H2S has been demonstrated in vascular smooth muscle cells (VSMCs), catalyzed by cystathionine γ-lyase (CSE). An elevated endogenous H2S level in animals leads to decreased blood pressure without altering heart rate. At physiologically relevant concentrations, H2S relaxes vascular tissues by directly acting on VSMCs. Inhibition of CSE induces a slowly developed hypertension. Increased endogenous production of H2S, on the other hand, reduces the contraction of isolated vascular tissues. The vasorelaxant effect of H2S is partially mediated by endothelium, but KATP channels in VSMCs are the major target of this gas. Dependent on the type of vascular tissue, the production of H2S and the mechanisms for the vasorelaxant effects of H2S vary. Vasorelaxation of resistant arteries induced by H2S is much greater than that of conduit arteries. Although the regulation of endogenous production of H2S in vascular tissues has been unclear, nitric oxide has been shown to increase H2S production in vascular tissues. Taking these novel observations together, the importance of H2S as a gasotransmitter in homeostatic control of cardiovascular function has been greatly appreciated. Accurate measurement of the endogenous level, in addition to the production rate, of H2S in cardiovascular tissues has not been achieved to date. Alterations in the production and function of endogenous H2S under different pathophysiological conditions have not been examined. Specific endogenous stimulators and inhibitors for H2S metabolism are still largely unknown. These encumbrances are not viewed as insurmountable obstacles but challenges and prospects through which future breakthroughs in the understanding of gasotransmitter biology and medicine will be made.