Attentuation of cardiovascular remodelling in DOCA-Salt rats by the Vasopeptidase inhibitor, Omapatrilat

Loch, David and Hoey, Andrew and Brown, Lindsay (2006) Attentuation of cardiovascular remodelling in DOCA-Salt rats by the Vasopeptidase inhibitor, Omapatrilat. Clinical and Experimental Hypertension, 28 (5). pp. 475-488. ISSN 1064-1963


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Omapatrilat, a vasopeptidase inhibitor, inhibits both neutral endopeptidase and angiotensin-
converting enzyme with similar potency. The aim of this study was to investigate whether omapatrilat prevents or reverses cardiovascular remodeling and hypertension
in deoxycorticosterone acetate (DOCA)-salt rats. Male Wistar rats (313 ± 2 g, n=114) were uninephrectomized (UNX) with or without further treatment with DOCA and 1%
NaCl in the drinking water. Compared with UNX control rats, DOCA-salt rats developed hypertension, cardiovascular hypertrophy, perivascular and interstitial cardiac
fibrosis and inflammation, endothelial dysfunction, and the prolongation of ventricular action potential duration within four weeks. The administration of omapatrilat (40 mg/
kg/day po) for two weeks commencing two weeks after surgery attenuated the development of cardiovascular hypertrophy, inflammation, fibrosis, and ventricular action potential prolongation. In contrast, omapatrilat treatment did not lower systolic blood pressure nor improve endothelial dysfunction. This study concludes that the reninangiotensin- aldosterone, natriuretic peptide, and bradykinin systems are directly involved in the pathogenesis of cardiovascular remodeling in the DOCA-salt model of hypertension in rats, which may be independent of their effects on blood pressure.

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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Deposited in accordance with the copyright policy of the publisher.
Faculty / Department / School: Historic - Faculty of Sciences - Department of Biological and Physical Sciences
Date Deposited: 11 Oct 2007 01:13
Last Modified: 02 Jul 2013 22:46
Uncontrolled Keywords: DOCA-salt rat, omapatrilat, hypertension, fibrosis, hypertrophy
Fields of Research : 06 Biological Sciences > 0606 Physiology > 060699 Physiology not elsewhere classified
Identification Number or DOI: 10.1080/10641960600798754

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