Document Detail

Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension.
MedLine Citation:
PMID:  20219858     Owner:  NLM     Status:  MEDLINE    
AIMS: Growing 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 RESULTS: Treatment of 25-week-old SHR with the arginase inhibitor N(omega)-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. CONCLUSION: Our 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.
Teddy Bagnost; Ling Ma; Rafaela F da Silva; Rana Rezakhaniha; Christophe Houdayer; Nikos Stergiopulos; Claire André; Yves Guillaume; Alain Berthelot; Céline Demougeot
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-10
Journal Detail:
Title:  Cardiovascular research     Volume:  87     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-16     Completed Date:  2010-11-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  569-77     Citation Subset:  IM    
Laboratoire de Physiologie - Pharmacologie - Nutrition - Préventive Expérimentale, Equipe Sciences Séparatives Biologiques et Pharmaceutiques, EA-4267, Faculté de Médecine-Pharmacie, Besançon, Place Saint-Jacques, Besançon cedex 25030, France.
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MeSH Terms
Aorta / drug effects,  enzymology,  physiopathology
Arginase / antagonists & inhibitors*,  metabolism
Arginine / analogs & derivatives*,  pharmacology
Blood Pressure / drug effects
Cardiovascular Agents / pharmacology*
Carotid Arteries / drug effects,  enzymology,  physiopathology
Collagen / metabolism
Cyclooxygenase 1 / metabolism
Cyclooxygenase 2 / metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects,  enzymology,  physiopathology
Enzyme Inhibitors / pharmacology*
Heart Diseases / enzymology,  pathology,  prevention & control
Hypertension / drug therapy*,  enzymology,  genetics,  pathology,  physiopathology
Membrane Proteins / metabolism
Mesenteric Arteries / drug effects,  enzymology,  physiopathology
Myocardium / pathology
Nitric Oxide Synthase / metabolism
Rats, Inbred SHR
Rats, Inbred WKY
Time Factors
Vasoconstriction / drug effects
Vasoconstrictor Agents / pharmacology
Vasodilation / drug effects
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Cardiovascular Agents; 0/Enzyme Inhibitors; 0/Membrane Proteins; 0/N(omega)-hydroxynorarginine; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 74-79-3/Arginine; 9007-34-5/Collagen; EC Oxide Synthase; EC 1; EC 2; EC protein, rat; EC protein, rat; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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