Regulation of cardiovascular cell function by hydrogen sulfide (H2S)

Since the discovery of endogenously-produced hydrogen sulfide (H2S) in various tissues, there has been an explosion of interest in H2S as a biological mediator alongside other gaseous mediators, nitric oxide and carbon monoxide. The identification of enzyme-regulated H2S synthetic pathways in the cardiovascular system has led to a number of studies examining specific regulatory actions of H2S. We review evidence showing that endogenously-generated and exogenously-administered H2S exerts a wide range of actions in vascular and myocardial cells including vasodilator/vasoconstrictor effects via modification of the smooth muscle tone, induction of apoptosis and anti-proliferative responses in the smooth muscle cells, angiogenic actions, effects relevant to inflammation and shock, and cytoprotection in models of myocardial ischemia-reperfusion injury. Several molecular mechanisms of action of H2S have been described. These include interactions of H2S with NO, redox regulation of multiple signaling proteins and regulation of K-ATP, channel opening. The gaps in our current understanding of precise mechanisms, the absence of selective pharmacological tools and the limited availability of H2S measurement techniques for living tissues, leave many questions about physiological and pathophysiological roles of H2S unanswered at present. Nevertheless, this area of investigation is advancing rapidly. We believe H2S holds promise as an endogenous mediator controlling a wide range of cardiovascular cell functions and integrated responses under both physiological and pathological conditions and may be amenable to therapeutic manipulation. Copyright (C) 2010 John Wiley & Sons, Ltd.