H₂S-induced vasorelaxation and underlying cellular and molecular mechanisms

TLDR

Hydrogen sulfide is endogenously produced in vascular smooth muscle cells. The study investigated the signal transduction pathways mediating hydrogen sulfide’s vascular effects. Hydrogen sulfide produced a concentration‑dependent relaxation of rat aortic rings that was preserved after denervation but diminished by endothelial removal, nitric‑oxide synthase inhibition, or Ca²⁺‑dependent K⁺ channel blockade; soluble guanylate cyclase inhibitors ODQ and NS‑2028 suppressed SNP but potentiated H₂S, an effect abrogated by superoxide dismutase, while Ca²⁺‑free conditions and prior H₂S exposure reduced SNP responsiveness, indicating that H₂S relaxes vessels via an endothelial‑dependent, extracellular Ca²⁺‑mediated, but cGMP‑independent mechanism.

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.