Effect of exogenous kappa-opioid receptor activation in rat model of myocardial infarction.

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Title Effect of exogenous kappa-opioid receptor activation in rat model of myocardial infarction.
Author Peart, Jason Nigel John; Gross, Eric R.; Gross, Garrett J.
Journal Name Journal of Cardiovascular Pharmacology
Year Published 2004
Place of publication United States
Publisher Lippincott Williams & Wilkins
Abstract The involvement of opioid receptor activation during ischemia-reperfusion is somewhat controversial. While it is generally accepted that activation of the 8-opioid receptor (DOR) is cardioprotective, and may indeed be an important mediator of ischemic preconditioning, the role of the K-opioid receptor (KOR) is less well understood. To this end, we examined three different KOR agonists and their effects upon infarct size and arrhythmia development. Male Sprague-Dawley rats were subjected to 30 minutes of occlusion followed by 90 minutes of reperfusion. Opioid receptor agonists were administered 10 minutes before the onset of ischemia, while the opioid antagonists were given 20 minutes before occlusion. Untreated rats exhibited an infarct size (IS/AAR%) of 52.4 ′ 2.7%. Pretreatment with the DOR agonist, BW373U86, limited infarct development to 37.2 ′ 1.8%, which was reversed by the selective DOR antagonist, BNTX. All three KOR agonists studied, U50,488, ICI 204,448, and BRL 52537 significantly reduced infarct size to levels comparable to that of BW373U86. The infarct-sparing effects of U50,488 and ICI 204,448 were abolished by the selective KOR antagonist, nor-BNI. Nor-BNI failed to inhibit the cardioprotective effects of BRL 52537. Furthermore, U50,488 and BRL 52537, but not ICI 204,448, significantly reduced the incidence of arrhythmias. These effects were not blocked by nor-BNI. These data demonstrate that KOR activation provides a similar degree of infarct size reduction as DOR activation. KOR agonists also reduced arrhythmogenesis; however, these responses appear to be independent of KOR activation.
Peer Reviewed Yes
Published Yes
Publisher URI http://journals.lww.com/cardiovascularpharm/pages/default.aspx
Alternative URI http://journals.lww.com/cardiovascularpharm/toc/2004/03000
Volume 43
Issue Number 3
Page from 410
Page to 415
ISSN 0160-2446
Date Accessioned 2006-07-26
Date Available 2009-12-16T07:11:22Z
Language en_AU
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Clinical Pharmacology and Therapeutics
URI http://hdl.handle.net/10072/27630
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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