| Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension. | |
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MedLine Citation:
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PMID: 20219858 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-10 |
Journal Detail:
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Title: Cardiovascular research Volume: 87 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-16 Completed Date: 2010-11-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
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Languages: eng Pagination: 569-77 Citation Subset: IM |
Affiliation:
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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 | |
Descriptor/Qualifier:
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Animals 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 Compliance Cyclooxygenase 1 / metabolism Cyclooxygenase 2 / metabolism Disease Models, Animal Dose-Response Relationship, Drug Endothelium, Vascular / drug effects, enzymology, physiopathology Enzyme Inhibitors / pharmacology* Fibrosis Heart Diseases / enzymology, pathology, prevention & control Hypertension / drug therapy*, enzymology, genetics, pathology, physiopathology Male Membrane Proteins / metabolism Mesenteric Arteries / drug effects, enzymology, physiopathology Myocardium / pathology Nitric Oxide Synthase / metabolism Rats Rats, Inbred SHR Rats, Inbred WKY Time Factors Vasoconstriction / drug effects Vasoconstrictor Agents / pharmacology Vasodilation / drug effects Vasodilator Agents / pharmacology |
| Chemical | |
Reg. No./Substance:
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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 1.14.13.39/Nitric Oxide Synthase; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Ptgs1 protein, rat; EC 1.14.99.1/Ptgs2 protein, rat; EC 3.5.3.1/Arginase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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