H2S-induced vasorelaxation and underlying cellular and molecular mechanisms

Abstract

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