Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats

Abstract

Hydrogen sulfide (H 2 S) has been shown recently to function as an important gasotransmitter. The present study investigated the vascular effects of H 2 S, both exogenously applied and endogenously generated, on resistance mesenteric arteries of rats and the underlying mechanisms. Both H 2 S and NaHS evoked concentration-dependent relaxation of in vitro perfused rat mesenteric artery beds (MAB). The sensitivity of MAB to H 2 S (EC 50, 25.2 ± 3.6 μM) was about fivefold higher than that of rat aortic tissues. Removal of endothelium or coapplication of charybdotoxin and apamin to endothelium-intact MAB significantly reduced the vasorelaxation effects of H 2 S. The H 2 S-induced relaxation of MAB was partially mediated by ATP-sensitive K+(K ATP) channel activity in vascular smooth muscle cells. Pinacidil (EC 50, 1.7 ± 0.1 μM, n = 6) mimicked, but glibenclamide (10 μM, n = 6) suppressed, the vasorelaxant effect of H 2 S. K ATP channel currents in isolated mesenteric artery smooth muscle cells were significantly augmented by H 2 S. l-Cysteine, a substrate of cystathionine-γ-lyase (CSE), at 1 mM increased endogenous H 2 S production by sixfold in rat mesenteric artery tissues and decreased contractility of MAB. dl-Propargylglycine (a blocker of CSE) at 10 μM abolished l-cysteine-dependent increase in H 2 S production and relaxation of MAB. Our results demonstrated a tissue-specific relaxant response of resistance arteries to H 2 S. The stimulation of K ATP channels in vascular smooth muscle cells and charybdotoxin/apamin-sensitive K+channels in vascular endothelium by H 2 S represents important cellular mechanisms for H 2 S effect on MAB. Our study also demonstrated that endogenous CSE can generate sufficient H 2 S from exogenous l-cysteine to cause vasodilation. Future studies are merited to investigate direct contribution of endogenous H 2 S to regulation of vascular tone.