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Antagonism of the antithrombotic and antiatherosclerotic actions of aspirin by rofecoxib in the cholesterol-fed rabbit.
MedLine Citation:
PMID:  21457221     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background and purpose: Most patients at elevated cardiovascular risk receive long-term aspirin (ASA) antiplatelet treatment. The present study specifically addresses the pharmacological interactions between selective cyclooxygenase (COX)-2 inhibitors and ASA and the possible consequences for the thrombotic risk during long-term treatment. Experimental approach: New Zealand white rabbits were fed for 12 weeks a standard laboratory diet supplemented with 1 % cholesterol (CON). Age-matched control rabbits were fed the same standard diet without addition of cholesterol (SD). Rabbits were randomly assigned to one of the following groups: rofecoxib (ROFE, 25 mg/kg, bid), acetylsalicylic acid (ASA, 5 mg/kg bid) or a combination of both (ASA + ROFE). At the end of the feeding period the severity of atherosclerotic plaque formation was assessed in the aorta. Thrombus formation was assessed in the left carotid artery using a modified Folts procedure. Key results: Treatment of cholesterol-fed rabbits with ASA significantly reduced plaque formation. This reduction in lesion size was completely abrogated by rofecoxib in animals treated with the combination of rofecoxib and ASA. In the modified Folts model treatment with either rofecoxib or ASA increased the total blood flow above that of untreated animals. This increase was statistically significant in case of ASA, while cotreatment with rofecoxib abolished this ASA effect completely and reduced the total flow rate to levels in untreated hypercholesterolemic controls. Conclusions: COX-2 inhibition by rofecoxib attenuates the antithrombotic and antiatherosclerotic effects of ASA during long-term treatment in cholesterol fed rabbits.
Authors:
G Kaber; B Kaiser; D Baumgärtel-Allekotte; Bh Rauch; S Noßmann; Kh Heim; Aa Weber; N Nagy; Jw Fischer; K Schrör
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-1
Journal Detail:
Title:  British journal of pharmacology     Volume:  -     ISSN:  1476-5381     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Institut für Pharmakologie und Klinische Pharmakologie der Heinrich-Heine-Universität, Düsseldorf ; Arbeitsgruppe Hämostaseologie der Friedrich-Schiller-Universität, Jena ; Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn , Institut für Pharmakologie des Universitätsklinikums Essen, Essen.
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