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

<h4>Background</h4>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...

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Autores principales: Lai Ming Yung, Wing Tak Wong, Xiao Yu Tian, Fung Ping Leung, Lai Hang Yung, Zhen Yu Chen, Xiaoqiang Yao, Chi Wai Lau, Yu Huang
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:cb0c2283e5b4413cb150519b7fcd3d682021-11-18T06:56:36ZInhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.1932-620310.1371/journal.pone.0017437https://doaj.org/article/cb0c2283e5b4413cb150519b7fcd3d682011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21479266/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>The novel findings highlight a significant therapeutic benefit of RAS blockade in the treatment of endothelial dysfunction-related vascular complications in postmenopausal states.Lai Ming YungWing Tak WongXiao Yu TianFung Ping LeungLai Hang YungZhen Yu ChenXiaoqiang YaoChi Wai LauYu HuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17437 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lai Ming Yung
Wing Tak Wong
Xiao Yu Tian
Fung Ping Leung
Lai Hang Yung
Zhen Yu Chen
Xiaoqiang Yao
Chi Wai Lau
Yu Huang
Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>The novel findings highlight a significant therapeutic benefit of RAS blockade in the treatment of endothelial dysfunction-related vascular complications in postmenopausal states.
format article
author Lai Ming Yung
Wing Tak Wong
Xiao Yu Tian
Fung Ping Leung
Lai Hang Yung
Zhen Yu Chen
Xiaoqiang Yao
Chi Wai Lau
Yu Huang
author_facet Lai Ming Yung
Wing Tak Wong
Xiao Yu Tian
Fung Ping Leung
Lai Hang Yung
Zhen Yu Chen
Xiaoqiang Yao
Chi Wai Lau
Yu Huang
author_sort Lai Ming Yung
title Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.
title_short Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.
title_full Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.
title_fullStr Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.
title_full_unstemmed Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.
title_sort inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/cb0c2283e5b4413cb150519b7fcd3d68
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