© 1996 American Heart Association, Inc.
Articles |
Morphine Mimics the Cardioprotective Effect of Ischemic Preconditioning via a Glibenclamide-Sensitive Mechanism in the Rat Heart
From the Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Correspondence to Garrett J. Gross, PhD, Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226.
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
µ- and 
-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 µg/kg IV) 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 IV), a
KATP channel antagonist, or naloxone (3 mg/kg
IV), 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.
Key Words: myocardial infarction • ATP-sensitive K+ channels • naloxone • opioid receptors
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