Activation of kappa-opioid receptors at reperfusion affords cardioprotection in both rat and mouse hearts.

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Title Activation of kappa-opioid receptors at reperfusion affords cardioprotection in both rat and mouse hearts.
Author Peart, Jason Nigel John; Gross, Eric R.; Reichelt, Melissa Elizabeth; Hsu, Anna; Headrick, John Patrick; Gross, Garrett J.
Journal Name Basic Research in Cardiology
Year Published 2008
Place of publication Germany
Publisher Dr. Dietrich Steinkopff Verlag
Abstract The temporal properties of kappa-opioid receptor (κ-OR) mediated cardioprotection are less well characterised than delta-opioid receptor (δ-OR) responses. This study was aimed at delineating the time course of κ-OR-mediated protection in two experimental models: an in vivo rat model of regional myocardial infarction (30 min of left coronary artery occlusion with 120 min of reperfusion), and an in vitro perfused murine heart model (undergoing 25 min of global ischemia and 45 min of reperfusion). In the rat model, the selective κ-OR agonist U50, 488 (0.1 mg/kg, IV bolus), administered either 10 min prior to ischemia or 5 min prior to reperfusion, significantly reduced infarct size (38 ± 3% and 43 ± 2% infarct size/area-at-risk (IS/AAR), respectively; P < 0.05) compared to untreated rats (56 ± 1% IS/AAR). Administration of U50, 488 10 s after onset of reperfusion failed to elicit protection. Cardioprotection with U50,448 administered immediately prior to reperfusion was abolished by a κ-OR antagonist, (0.1 mg/kg nor-BNI), given 10 min prior to reperfusion. In the in vitro murine model, untreated hearts exhibited 28 ± 2% (IS/AAR) infarct size. Infusion of U50, 488 (at a final 100 nM concentration) significantly limited infarct size in mouse hearts when applied at the onset of reperfusion (15 ± 2% IS/AAR; P < 0.05), yet failed to afford protection when infused prior to ischemia. Additionally, in both models studied, treatment with either wortmannin or 5-hydroxydecanoate (5-HD) abrogated the protective effects of U50,488 applied just prior to reperfusion. In summary, κ-ORs afford cardioprotection primarily when activated prior to and not after reperfusion. This protection may involve activation of the PI3 kinase (PI3K) pathway and mitochondrial (mito) K ATP channels.
Peer Reviewed Yes
Published Yes
Alternative URI
Volume 103
Issue Number 5
Page from 454
Page to 463
ISSN 0300-8428
Date Accessioned 2008-10-01
Language en_AU
Research Centre Menzies Health Institute Qld; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Clinical Pharmacology and Therapeutics; PRE2009-Medical and Health Sciences
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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