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Hydrogen sulfide (H2S) is an endogenously gaseous messenger with a number of physiological effects. Pharmacological and genetic models point toward an important role for this vasodilator gas in the regulation of vascular tone, cardiac response to ischemia/reperfusion injury, and inflammation among others. Understanding the complex interaction of H2S with basic cellular signaling and its impact on endothelial and smooth muscle physiology may provide insights into the early stages of developing vascular inflammation and atherosclerosis or related vascular pathologies. The underlying mechanism of action is not completely understood.