title: 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 H2S 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 H2S 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 H2S prevents activation of BMP4/COX-2 pathway in hypertension, which may be involved in the ameliorative effect of H2S on endothelial impairment. These results throw light on endothelial protective effect of H2S and provide new target for prevention and therapy of hypertension.
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Animal Science, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Lin
authors.identifier: 0000-0002-2876-0007
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Jing-Hui
authors.identifier: 0000-0001-7891-9453
authors.initials: JH
authors.lastname: Dong
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Sheng
authors.identifier: 0000-0001-7777-9700
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Animal Science, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Hong-Mei
authors.identifier: 0000-0002-9571-0843
authors.initials: HM
authors.lastname: Xue
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Qi
authors.identifier: 0000-0001-6762-2929
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Animal Science, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Xu
authors.identifier: 0000-0003-2206-8308
authors.initials: X
authors.lastname: Teng
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang 050017, China; Key Laboratory of Vascular Medicine of Hebei Province, Shijiazhuang 050017, China.
authors.forename: Yu-Ming
authors.identifier: 0000-0002-3282-056X
authors.initials: YM
authors.lastname: Wu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055415:Bone Morphogenetic Protein 4; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D006862:Hydrogen Sulfide