The vasorelaxant effect of H2S as a novel endogenous gaseous K-ATP channelopener

Hydrogen sulfide (H2S) has been traditionally viewed as a toxic gas. It is also, however, endogenously generated from cysteine metabolism. We attempte d to assess the physiological role of H2S in the regulation of vascular con tractility, the modulation of H2S production in vascular tissues, and the u nderlying mechanisms. Intravenous bolus injection of H2S transiently decrea sed blood pressure of rats by 12- 30 mmHg, which was antagonized by prior b lockade of K-ATP channels. H2S relaxed rat aortic tissues in vitro in a K-A TP channel-dependent manner. In isolated vascular smooth muscle cells (SMCs ), H2S directly increased K-ATP channel currents and hyperpolarized membran e. The expression of H2S-generating enzyme was identified in vascular SMCs, but not in endothelium. The endogenous production of H2S from different va scular tissues was also directly measured with the abundant level in the or der of tail artery, aorta and mesenteric artery. Most importantly, H2S prod uction from vascular tissues was enhanced by nitric oxide. Our results demo nstrate that H2S is an important endogenous vasoactive factor and the first identified gaseous opener of K-ATP channels in vascular SMCs.