Ischemic preconditioning and morphine-induced cardioprotection involve the delta (delta) opioid receptor in the intact rat heart

被引:203
作者
Schultz, JJ [1 ]
Hsu, AK [1 ]
Gross, GJ [1 ]
机构
[1] MED COLL WISCONSIN, DEPT PHARMACOL & TOXICOL, MILWAUKEE, WI 53226 USA
关键词
myocardial protection; naltrindole; delta-opioid receptors; morphine; ischemic preconditioning;
D O I
10.1006/jmcc.1997.0454
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Several investigators have demonstrated that the opioid pathway is involved in tissue preservation during hypoxia or ischemia and that this protection is mediated via the delta (delta)-opioid receptor. Subsequently we have shown that opioid receptors are involved in ischemic preconditioning (PC) in the rat heart and that morphine produces a cardioprotective effect; however, the class of opioid receptors involved in mediating these effects is still unknown. Therefore, the purpose of the present study was to test the hypothesis that ischemia- and morphine-induced cardioprotection are mediated via stimulation of the delta-opioid receptor in the rat heart, Anesthetized, open-chest Wistar rats were subjected to one of six protocols, The control group was subjected to 30 min of occlusion and 2 h of reperfusion. Ischemic PC was elicited by three 5 min occlusion periods interspersed with 5 min of reperfusion, Morphine-induced cardioprotection was produced by three 5 min morphine infusions (100 mu g/kg/infusion. i.v.) interspersed with a 5-min drug-free period. To determine if the delta-opioid receptor has a role in ischemic PC and morphine-induced cardioprotection, naltrindole (NTI), a selective delta-opioid receptor antagonist, was utilized. NTI (5 mg/kg, i.v.) was given 10 min prior to ischemic PC (NTI+PC) or morphine infusion (NTI+MOR). Also, NTI (5 mg/kg, i.v.) was given 10 min before the 30 min occlusion period in untreated rats. Infarct size (IS) as a percent of the area at risk (AAR) was determined by 2,3,5-triphenyltetrazolium chloride staining. Ischemic PC and morphine infusions resulted in similar reductions in IS/AAR from 51+/-4 to 11+/-3 and 15+/-4%, (*P<0.05), respectively. NTI completely abolished the cardioprotective effect induced by ischemia and morphine, The results of the present study suggests a role of delta-opioid receptors in ischemic PC or morphine-induced myocardial protection in the rat. (C) 1997 Academic Press Limited.
引用
收藏
页码:2187 / 2195
页数:9
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