|Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension.|
|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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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-10|
|Title: Cardiovascular research Volume: 87 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2010 Aug|
|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|
|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.|
|APA/MLA Format Download EndNote Download BibTex|
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
Vasoconstriction / drug effects
Vasoconstrictor Agents / pharmacology
Vasodilation / drug effects
Vasodilator Agents / pharmacology
|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 188.8.131.52/Nitric Oxide Synthase; EC 184.108.40.206/Cyclooxygenase 1; EC 220.127.116.11/Cyclooxygenase 2; EC 18.104.22.168/Ptgs1 protein, rat; EC 22.214.171.124/Ptgs2 protein, rat; EC 126.96.36.199/Arginase|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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