H2S-induced vasorelaxation and underlying cellular and molecular mechanisms

H2S is endogenously generated in vascular smooth muscle cells. The signal transduction pathways involved in the vascular effects of H2S have been unclear and were investigated in the present study. H2S induced a concentration-dependent relaxation of rat aortic tissues that was not affected by vascular denervation. The vasorelaxant potency of H2S was attenuated by the removal of the endothelium. Similarly, the blockade of nitric oxide synthase or the coapplication of the Ca2+-dependent K+ channel blockers apamin and charybdotoxin reduced the H2S-induced relaxation of the endothelium-intact aortic tissues. Sodium nitroprusside (SNP)-induced relaxation was completely abolished by either H-1-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) or NS-2028, two soluble guanylate cyclase inhibitors. Instead of inhibition, ODQ and NS-2028 potentiated the H2S-induced vasorelaxation, which was suppressed by superoxide dismutase. The vasorelaxant effect of H2S was also significantly attenuated when Ca2+-free bath solution was used. Finally, pretreatment of aortic tissues with H2S reduced the relaxant response of vascular tissues to SNP. Our results demonstrate that the vascular effect of H2S is partially mediated by a functional endothelium and dependent on the extracellular calcium entry but independent of the activation of the cGMP pathway.