title: Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.
abstract: BACKGROUND
  Estrogen deficiency increases the cardiovascular risks in postmenopausal women. Inhibition of the renin-angiotensin system (RAS) and associated oxidative stress confers a cardiovascular protection, but the role of RAS in estrogen deficiency-related vascular dysfunction is unclear. The present study investigates whether the up-regulation of RAS and associated oxidative stress contributes to the development of endothelial dysfunction during estrogen deficiency in ovariectomized (OVX) rats.
  
  
  RESULTS
  Adult female rats were ovariectomized with and without chronic treatment with valsartan and enalapril. Isometric force measurement was performed in isolated aortae. The expression of RAS components was determined by immunohistochemistry and Western blotting method while ROS accumulation in the vascular wall was evaluated by dihydroethidium fluorescence. Ovariectomy increased the expression of angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT(1)R), NAD(P)H oxidase, and nitrotyrosine in the rat aorta. An over-production of angiotensin II and ROS was accompanied by decreased phosphorylation of eNOS at Ser(1177) in OVX rat aortae. These pathophysiological changes were closely coupled with increased oxidative stress and decreased nitric oxide bioavailability, culminating in markedly impaired endothelium-dependent relaxations. Furthermore, endothelial dysfunction and increased oxidative stress in aortae of OVX rats were inhibited or reversed by chronic RAS inhibition with enalapril or valsartan.
  
  
  CONCLUSIONS
  The novel findings highlight a significant therapeutic benefit of RAS blockade in the treatment of endothelial dysfunction-related vascular complications in postmenopausal states.
authors.affiliation: Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Lai Ming
authors.initials: LM
authors.lastname: Yung
authors.forename: Wing Tak
authors.initials: WT
authors.lastname: Wong
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Tian
authors.forename: Fung Ping
authors.initials: FP
authors.lastname: Leung
authors.forename: Lai Hang
authors.initials: LH
authors.lastname: Yung
authors.forename: Zhen Yu
authors.initials: ZY
authors.lastname: Chen
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Lau
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D004656:Enalapril / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D004967:Estrogens / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004967:Estrogens; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D004656:Enalapril; D000068756:Valsartan; D019255:NADPH Oxidases; D007703:Peptidyl-Dipeptidase A; D014633:Valine; D000109:Acetylcholine