H(2)S-induced vasorelaxation and underlying cellular and molecular mechanisms.
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 1H-[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.
Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E5.
Weimin
W
Zhao
Rui
R
Wang
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000294:innervation / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003714:Denervation; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D005740:Gases; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000008:administration & dosage / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D005740:Gases; D020030:Nitric Oxide Donors; D013440:Sulfides; D014665:Vasodilator Agents; D009599:Nitroprusside; C025451:sodium bisulfide; D006152:Cyclic GMP; D002118:Calcium; D006862:Hydrogen Sulfide