| Pravastatin normalizes EDCF-mediated response via suppression of Rho-kinase signalling in mesenteric artery from aged type 2 diabetic rat. | |
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MedLine Citation:
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PMID: 22212448 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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AIM: Although pravastatin has known pleiotropic effects against adverse cardiovascular conditions, little is known about its effects on endothelium-derived contracting factor (EDCF)-mediated signalling. We aimed to determine the effects of pravastatin on the production of and responses to EDCF in superior mesenteric arteries isolated from rats at the chronic stage of type 2 diabetes. METHODS: Contractions to acetylcholine (ACh) were examined in superior mesenteric artery rings from aged type 2 diabetic Otsuka Long-Evans Fatty (OLETF) rats (56-60 weeks old), from control age-matched non-diabetic Long-Evans Tokushima Otsuka (LETO) rats and from pravastatin-treated (10 mg/kg, p.o., daily for 4 weeks) OLETF rats. Mesenteric artery expressions of cyclo-oxygenases (COXs), microsomal-PGE synthases (mPGESs), RhoA and Rho-kinase proteins, and also the level of phosphorylated ezrin, radixin and moesin (PERM), a substrate for Rho-kinase, were detected by western blotting. RESULTS: Arteries from OLETF rats exhibited (vs. LETO rats): 1) enhanced ACh-induced EDCF-mediated contractions, which were inhibited by the Rho-kinase inhibitor Y27632; 2) reductions in the ACh-stimulated release of both PGE(2) and superoxide; 3) increased COX-1 and PERM protein expressions. Mesenteric arteries from OLETF rats treated with pravastatin exhibited (vs. untreated OLETF): 1) reduced ACh-induced contraction; 2) suppressed ACh-induced PGE(2) production and superoxide generation; 3) reduced ACh-induced PERM protein expression. CONCLUSIONS: These results suggest that pravastatin exerts beneficial effects against abnormal EDCF signalling by suppressing Rho-kinase and promoting antioxidant activity in the mesenteric arteries of rats at the chronic stage of type 2 diabetes. |
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Authors:
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Keiko Ishida; Takayuki Matsumoto; Kumiko Taguchi; Katsuo Kamata; Tsuneo Kobayashi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-28 |
Journal Detail:
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Title: Acta physiologica (Oxford, England) Volume: - ISSN: 1748-1716 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2012-1-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101262545 Medline TA: Acta Physiol (Oxf) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2011 The Authors Acta Physiologica © 2011 Scandinavian Physiological Society. |
Affiliation:
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Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, 142-8501, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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