Attenuation of cardiovascular remodeling in DOCA-salt rats by the vasopeptidase inhibitor, omapatrilat

Loch, David, Hoey, Andrew and Brown, Lindsay (2006) Attenuation of cardiovascular remodeling in DOCA-salt rats by the vasopeptidase inhibitor, omapatrilat. Clinical and Experimental Hypertension, 28 5: 475-488. doi:10.1080/10641960600798754


Author Loch, David
Hoey, Andrew
Brown, Lindsay
Title Attenuation of cardiovascular remodeling in DOCA-salt rats by the vasopeptidase inhibitor, omapatrilat
Journal name Clinical and Experimental Hypertension   Check publisher's open access policy
ISSN 1064-1963
1525-6006
Publication date 2006
Sub-type Article (original research)
DOI 10.1080/10641960600798754
Volume 28
Issue 5
Start page 475
End page 488
Total pages 14
Editor Mustafa Lokhandwala
Place of publication Philadelphia, PA, United States
Publisher Taylor & Francis
Collection year 2006
Language eng
Subject C1
320502 Basic Pharmacology
730106 Cardiovascular system and diseases
Abstract 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 renin-angiotensin-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.
Keyword Doca-salt Rat
Omapatrilat
Hypertension
Fibrosis
Hypertrophy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 08:27:00 EST