Hydrogen Sulfide Improves Endothelial Dysfunction via Downregulating BMP4/COX-2 Pathway in Rats with Hypertension

Abstract

Aims. We object to elucidate that protective effect of H ₂S on endothelium is mediated by downregulating BMP4 (bone morphogenetic protein 4)/cyclooxygenase- (COX-) 2 pathway in rats with hypertension. Methods and Results. The hypertensive rat model induced by two-kidney one-clip (2K1C) model was used. Exogenous NaHS administration (56  μmol/kg/day, intraperitoneally once a day) reduced mean arterial pressure (MAP) of 2K1C rats from 199.9 ± 3.312 mmHg to 159.4 ± 5.434 mmHg, while NaHS did not affect the blood pressure in the Sham rats and ameliorated endothelium-dependent contractions (EDCs) of renal artery in 2K1C rats. 2K1C reduced CSE level twofold, decreased plasma levels of H ₂S about 6-fold, increased BMP4, Nox2, and Nox4 levels 2-fold and increased markers of oxidative stress MDA and nitrotyrosine 1.5-fold, upregulated the expression of phosphorylation-p38 MAPK 2-fold, and increased protein levels of COX-2 1.5-fold, which were abolished by NaHS treatment. Conclusions. Our results demonstrate that H ₂S prevents activation of BMP4/COX-2 pathway in hypertension, which may be involved in the ameliorative effect of H ₂S on endothelial impairment. These results throw light on endothelial protective effect of H ₂S and provide new target for prevention and therapy of hypertension.