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Connective tissue growth factor induction in a pressure-overloaded heart ameliorated by the angiotensin II type 1 receptor blocker olmesartan.
MedLine Citation:
PMID:  20944640     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Connective tissue growth factor (CTGF) is a secreted protein that regulates fibrosis. We hypothesized that CTGF is induced in a pressure-overloaded (PO) heart and that blocking the angiotensin II type 1 receptor would reduce CTGF expression. Accordingly, we administered olmesartan and compared its effects with other antihypertensive drugs in a PO heart. CTGF induction was determined in a rat PO model, and olmesartan, hydralazine or saline was continuously administered. The effects of olmesartan on CTGF induction, myocyte hypertrophy and fibrosis were evaluated. The effect of olmesartan on cardiac function was also examined in CTGF- and transforming growth factor-beta 1 (TGF-β1)-infused rats. CTGF was increased in the PO heart 3 days after aortic banding and was markedly distributed around the perivascular fibrotic area. After 28 days, blood pressure was not significantly different in the olmesartan and hydralazine groups, but olmesartan treatment reduced CTGF distribution in PO hearts. Olmesartan was associated with a significantly reduced myocyte hypertrophy index (4.77±0.48 for olmesartan and 6.05±1.45 for saline, P<0.01), fibrosis area (32.0±15.5% compared with the saline group, P<0.05) and serum TGF-β1 level (62.6±10.6 ng ml⁻¹ for olmesartan and 84.4±7.2 ng ml⁻¹ for hydralazine, P<0.05). In addition, cardiac function was significantly preserved in the olmesartan group compared with the saline group. Finally, olmesartan ameliorated the cardiac dysfunction in CTGF- and TGF-β1-infused rats. Olmesartan attenuated CTGF induction, reduced perivascular fibrosis and ameliorated cardiac dysfunction in a PO heart. Our results provide insight into the beneficial effects of olmesartan on PO hearts, independent of blood-pressure lowering.
Authors:
Mutsumi Iwamoto; Satoshi Hirohata; Hiroko Ogawa; Takashi Ohtsuki; Ryoko Shinohata; Toru Miyoshi; Faruk O Hatipoglu; Shozo Kusachi; Kazuhide Yamamoto; Yoshifumi Ninomiya
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-14
Journal Detail:
Title:  Hypertension research : official journal of the Japanese Society of Hypertension     Volume:  33     ISSN:  1348-4214     ISO Abbreviation:  Hypertens. Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307690     Medline TA:  Hypertens Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1305-11     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.
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