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Am J Physiol Heart Circ Physiol 280: H384-H391, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 1, H384-H391, January 2001

kappa - but not delta -opioid receptors mediate effects of ischemic preconditioning on both infarct and arrhythmia in rats

Guan-Ying Wang, Song Wu, Jian-Ming Pei, Xiao-Chun Yu, and Tak-Ming Wong

Department of Physiology and Institute of Cardiovascular Sciences and Medicine, Faculty of Medicine, University of Hong Kong, Hong Kong

Two series of experiments were performed in the isolated perfused rat heart to determine the role of kappa - and delta -opioid receptors (OR) in cardioprotection of ischemic preconditioning (IP). In the first series of experiments, it was found that IP with two cycles of 5-min regional ischemia followed by 5-min reperfusion each reduced infarct size induced by 30-min ischemia, and the ameliorating effect of IP on infarct was attenuated with blockade of either 5 × 10-6 mol/l nor-binaltorphimine (nor-BNI), a selective kappa -OR antagonist, or 5 × 10-6 mol/l naltrindole (NTD), a selective delta -OR antagonist. The second series showed that U50,488H, a selective kappa -OR agonist, or D-Ala2-D-leu5-enkephalin (DADLE), a selective delta -OR agonist, dose dependently reduced the infarct size induced by ischemia, which mimicked the effects of IP. The effect of 10-5 mol/l U50,488H on infarct was significantly attenuated by blockade of protein kinase C (PKC) with specific PKC inhibitors, 5 × 10-6 mol/l chelerythrine or 8 × 10-7 mol/l calphostin C, as well as by blockade of ATP-sensitive K+ (KATP) channels with blockers of the channel, 10-5 mol/l glibenclamide or 10-4 mol/l 5-hydroxydecanoate. IP also reduced arrhythmia induced by ischemia. Nor-BNI, but not NTD, attenuated, while U50,488H, but not DADLE, mimicked the antiarrhythmic action of IP. In conclusion, the present study has provided first evidence that kappa -OR mediates the ameliorating effects of IP on infarct and arrhythmia induced by ischemia, whereas delta -OR mediates the effects only on infarct. Both PKC and KATP channels mediate the effect of activation of kappa -OR on infarct.

opioid receptor; protein kinase C; ATP-sensitive potassium channel


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