title: Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide-sensitive mechanism in the rat heart.
abstract: Previous results from our laboratory have suggested that opioid receptors are involved in ischemic preconditioning (PC) in rat heart. Furthermore, other investigators have suggested that mu- and delta-opioid receptors mediate analgesia and hypoxic cerebral vasodilatation via opening of ATP-sensitive K+ (KATP) channels. Thus, the purpose of the present study was to test the hypothesis that activation of opioid receptors mimics the cardioprotective effect of ischemic PC and that this effect is produced by activation of KATP channels in the rat heart. Anesthetized open-chest Wistar rats were subjected to six different protocols. All groups were subjected to 30 minutes of occlusion and 2 hours of reperfusion. Ischemic PC was elicited by three 5-minute occlusion periods interspersed with 5 minutes of reperfusion. Similarly, morphine-induced PC was elicited by three 5-minute drug infusions (100 micrograms/kg i.v. ) interspersed with 5-minute drug-free periods before the prolonged 30-minute occlusion. Infarct size (IS) as a percentage of the area at risk (AAR) was determined by triphenyltetrazolium staining. Ischemic PC and morphine infusions resulted in similar reductions in IS/AAR from 56 +/- 5% to 11 +/- 3% and 12 +/- 5%, respectively (P < .05). Administration of glibenclamide (0.3 mg/kg i.v.), a KATP channel antagonist, or naloxone (3 mg/kg i.v.), a nonselective opioid receptor antagonist, both blocked the cardioprotective effects of morphine. These results indicate that opioid receptor stimulation results in a reduction in infarct size similar to that produced by ischemic PC. The effect of morphine is most likely mediated via an opioid receptor-KATP channel-linked mechanism in the rat heart, since glibenclamide abolished its protection.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Schultz
authors.forename: A K
authors.initials: AK
authors.lastname: Hsu
authors.forename: G J
authors.initials: GJ
authors.lastname: Gross
mesh_terms: D000818:Animals; D005905:Glyburide / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology
chemical_list: D015221:Potassium Channels; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine; D005905:Glyburide