Regulation of cardiovascular cell function by hydrogen sulfide (H(2)S).
Since the discovery of endogenously-produced hydrogen sulfide (H(2)S) in various tissues, there has been an explosion of interest in H(2)S as a biological mediator alongside other gaseous mediators, nitric oxide and carbon monoxide. The identification of enzyme-regulated H(2)S synthetic pathways in the cardiovascular system has led to a number of studies examining specific regulatory actions of H(2)S. We review evidence showing that endogenously-generated and exogenously-administered H(2)S 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 H(2)S have been described. These include interactions of H(2)S 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 H(2)S measurement techniques for living tissues, leave many questions about physiological and pathophysiological roles of H(2)S unanswered at present. Nevertheless, this area of investigation is advancing rapidly. We believe H(2)S 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.
Elsey
David J
DJ
Cardiff University, UK.
Fowkes
Robert C
RC
Baxter
Gary F
GF
D000818:Animals; D001794:Blood Pressure; D002417:Cattle; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats
D018836:Inflammation Mediators; D054086:KATP Channels; D009569:Nitric Oxide; D006862:Hydrogen Sulfide