Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats

• Published in: PloS one Vol. 6; no. 3; p. e17437
• Main Authors: Yung, Lai Ming, Wong, Wing Tak, Tian, Xiao Yu, Leung, Fung Ping, Yung, Lai Hang, Chen, Zhen Yu, Yao, Xiaoqiang, Lau, Chi Wai, Huang, Yu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.03.2011; Public Library of Science (PLoS)
• Subjects: Acetylcholine - pharmacology; Angiotensin; Angiotensin II; Angiotensin II - metabolism; Angiotensins; Animals; Aorta; Bioavailability; Biology; Cardiovascular diseases; Cardiovascular system; Catheters; Complications; Enalapril - pharmacology; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Endothelium, Vascular - physiopathology; Estrogens; Estrogens - deficiency; Estrogens - metabolism; Female; Fluorescence; Force measurement; Free Radical Scavengers - metabolism; Health risks; Health sciences; Hormone replacement therapy; Hypertension; Immunohistochemistry; Inhibition; Isometric; Medicine; Menopause; NAD; NAD(P)H oxidase; NADPH Oxidases - metabolism; Nitric oxide; Nitric Oxide - metabolism; Nitrotyrosine; Older people; Osteoporosis; Ovariectomy; Oxidases; Oxidative stress; Oxidative Stress - drug effects; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - metabolism; Phenols (Class of compounds); Phosphorylation; Physiology; Post-menopause; Postmenopausal women; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptor, Angiotensin, Type 1 - metabolism; Receptor, Angiotensin, Type 2 - metabolism; Renin; Renin-angiotensin system; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; Rodents; Smooth muscle; Tetrazoles - pharmacology; Valine - analogs & derivatives; Valine - pharmacology; Valsartan; Vasodilation - drug effects; Western blotting; Womens health; Hong Kong China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0017437

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. 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. The novel findings highlight a significant therapeutic benefit of RAS blockade in the treatment of endothelial dysfunction-related vascular complications in postmenopausal states.