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Enhanced cyclooxygenase 2-mediated vasorelaxation in coronary arteries from insulin-resistant obese Zucker rats.
MedLine Citation:
PMID:  20956003     Owner:  NLM     Status:  In-Process    
Obesity and metabolic syndrome increase the risk of coronary heart disease and lead to a proinflammatory state of the vascular wall. Endothelial dysfunction is associated with up-regulation of cyclooxygenase-2 (COX-2) and enhanced synthesis of constrictor prostaglandins in systemic arteries in diabetes. The present study assessed whether changes in the arachidonic acid (AA) metabolism via COX-1 and COX-2 may affect endothelial function of coronary arteries in obesity. Intramyocardial arteries from obese Zucker rats (OZR) and from lean Zucker rats (LZR) were mounted in microvascular myographs to assess vascular function and COX expression was determined by both immunohistochemistry and Western blot. AA elicited relaxations of similar magnitude in arteries from LZR and OZR which were abolished by endothelial cell removal. Selective inhibition of COX-1 enhanced the AA relaxant responses and inhibited the 5-hydroxytryptamine (5-HT)-induced vasoconstriction in arteries from both LZR and OZR. Antagonism of the TXA(2)/PGH(2) (TP) receptor mimicked the effects of COX-1 blockade in arteries from LZR but not OZR. Selective inhibition of COX-2 markedly reduced the vasodilatation induced by AA in OZR, but not in LZR, without altering 5-HT or ACh responses. COX-1 was widely distributed throughout the endothelial layer of coronary arteries from both LZR and OZR, while COX-2 protein, which was predominantly expressed in the endothelium, was significantly increased in arteries from OZR. Whereas AA is mainly metabolised to vasoconstrictor prostanoids via COX-1 in coronary arteries from healthy animals, endothelial COX-2 is up-regulated to produce vasodilator prostaglandins thus protecting coronary arteries in insulin resistant obese rats.
Ana Sánchez; Cristina Contreras; Pilar Martínez; Nuria Villalba; Sara Benedito; Albino García-Sacristán; Mercedes Salaíces; Medardo Hernández; Dolores Prieto
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-29
Journal Detail:
Title:  Atherosclerosis     Volume:  213     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  392-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Department of Physiology, Faculty of Pharmacy, Universidad Complutense de Madrid, Madrid 28040, Spain.
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