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Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension

Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully... AimsGrowing evidence suggests that arginase misregulation plays a key role in the pathophysiology of essential hypertension. In the present study, we investigated the potential cardiovascular therapeutic effects of a long-term treatment with an arginase inhibitor in adult spontaneously hypertensive rats (SHR) with fully developed hypertension.Methods and resultsTreatment of 25-week-old SHR with the arginase inhibitor N-hydroxy-nor-l-arginine (nor-NOHA, 40 mg/day for 10 weeks) sustainably reduced systolic blood pressure (30 mmHg, P < 0.05). The antihypertensive effect of nor-NOHA was associated with changes on mesenteric artery reactivity including the restoration of angiotensin-II-induced contraction and acetylcholine-induced vasodilation to the values of normotensive Wistar Kyoto rats. Both nitric oxide synthase and cyclooxygenase-dependent mechanisms account for the improvement of endothelial function afforded by the arginase inhibitor, which in addition blunted hypertension-induced endothelial arginase I overexpression in mesenteric arteries. Nor-NOHA also prevented the remodelling of aorta as measured by collagen content and media/lumen ratio, and improved the compliance of carotid artery in SHR. Cardiac fibrosis assessed by collagen content of left heart ventricle was reduced by nor-NOHA, with no significant effect on cardiac hypertrophy.ConclusionOur results report that a long-term treatment with an arginase inhibitor reduced blood pressure, improved vascular function, and reduced cardiac fibrosis in SHR with fully developed hypertension. These data suggest that arginase represents a promising novel target for pharmacological intervention in essential hypertension. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cardiovascular Research Oxford University Press

Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension

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References (50)

Publisher
Oxford University Press
Copyright
Published on behalf of the European Society of Cardiology. All rights reserved. The Author 2010. For permissions please email: journals.permissionsoxfordjournals.org.
Subject
ORIGINAL ARTICLES
ISSN
0008-6363
eISSN
1755-3245
DOI
10.1093/cvr/cvq081
pmid
20219858
Publisher site
See Article on Publisher Site

Abstract

AimsGrowing evidence suggests that arginase misregulation plays a key role in the pathophysiology of essential hypertension. In the present study, we investigated the potential cardiovascular therapeutic effects of a long-term treatment with an arginase inhibitor in adult spontaneously hypertensive rats (SHR) with fully developed hypertension.Methods and resultsTreatment of 25-week-old SHR with the arginase inhibitor N-hydroxy-nor-l-arginine (nor-NOHA, 40 mg/day for 10 weeks) sustainably reduced systolic blood pressure (30 mmHg, P < 0.05). The antihypertensive effect of nor-NOHA was associated with changes on mesenteric artery reactivity including the restoration of angiotensin-II-induced contraction and acetylcholine-induced vasodilation to the values of normotensive Wistar Kyoto rats. Both nitric oxide synthase and cyclooxygenase-dependent mechanisms account for the improvement of endothelial function afforded by the arginase inhibitor, which in addition blunted hypertension-induced endothelial arginase I overexpression in mesenteric arteries. Nor-NOHA also prevented the remodelling of aorta as measured by collagen content and media/lumen ratio, and improved the compliance of carotid artery in SHR. Cardiac fibrosis assessed by collagen content of left heart ventricle was reduced by nor-NOHA, with no significant effect on cardiac hypertrophy.ConclusionOur results report that a long-term treatment with an arginase inhibitor reduced blood pressure, improved vascular function, and reduced cardiac fibrosis in SHR with fully developed hypertension. These data suggest that arginase represents a promising novel target for pharmacological intervention in essential hypertension.

Journal

Cardiovascular ResearchOxford University Press

Published: Aug 1, 2010

Keywords: Arginase Arteries Endothelial function Remodelling Spontaneously hypertensive rat

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