The Gasotransmitter Role of Hydrogen Sulfide

Abstract

A novel concept of "gasotransmitter" arrived recently. Gasotransmitters are small molecules of endogenous gases with important physiological functions. Their production and metabolism are enzymatically regulated, and their effects are not dependent on specific membrane receptors. Following the identification of nitric oxide and carbon monoxide as gasotransmitters, hydrogen sulfide (H(2)S) may be qualified as the third gasotransmitter. Recent studies have shown that H(2)S is generated from vascular smooth muscle cells (SMCs), catalyzed by specific H(2)S-generating enzyme. At physiologically relevant concentrations, H(2)S relaxes vascular tissues, an effect mediated by the activation of ATP-sensitive K(+) (K(ATP)) channels in vascular SMCs. H(2)S directly alters the activity of K(ATP) channels without the involvement of second messengers. Furthermore, the endogenous production of H(2)S in the cardiovascular system is likely regulated by nitric oxide, whereas the vasorelaxant effect of nitric oxide is inhibited by H(2)S. It is anticipated that future studies will better reveal the molecular mechanisms underlying the effect of H(2)S on K(ATP) channel proteins, the interaction of H(2)S and other gasotransmitters in cardiovascular system, the endogenous stimulators and inhibitors of H(2)S metabolism, the role of H(2)S in the regulation of heart function, and the abnormal H(2)S production and action under various pathophysiological conditions.