Faculty Collaboration Database

Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide-sensitive mechanism in the rat heart. Circ Res 1996 Jun;78(6):1100-4

Date

06/01/1996

Pubmed ID

8635241

DOI

10.1161/01.res.78.6.1100

Scopus ID

2-s2.0-0029886874 (requires institutional sign-in at Scopus site)   385 Citations

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.

Author List

Schultz JE, Hsu AK, Gross GJ

MESH terms used to index this publication - Major topics in bold

Animals
Glyburide
Heart
Hemodynamics
Male
Morphine
Myocardial Ischemia
Naloxone
Potassium Channels
Rats
Rats, Wistar
Receptors, Opioid