The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener

Abstract

Hydrogen sulfide (H₂S) has been traditionally viewed as a toxic gas. It is also, however, endogenously generated from cysteine metabolism. We attempted to assess the physiological role of H₂S in the regulation of vascular contractility, the modulation of H₂S production in vascular tissues, and the underlying mechanisms. Intravenous bolus injection of H₂S transiently decreased blood pressure of rats by 12–30 mmHg, which was antagonized by prior blockade of K_ATP channels. H₂S relaxed rat aortic tissues in vitro in a K_ATP channel‐dependent manner. In isolated vascular smooth muscle cells (SMCs), H₂S directly increased K_ATP channel currents and hyperpolarized membrane. The expression of H₂S‐generating enzyme was identified in vascular SMCs, but not in endothelium. The endogenous production of H₂S from different vascular tissues was also directly measured with the abundant level in the order of tail artery, aorta and mesenteric artery. Most importantly, H₂S production from vascular tissues was enhanced by nitric oxide. Our results demonstrate that H₂S is an important endogenous vasoactive factor and the first identified gaseous opener of K_ATP channels in vascular SMCs.