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Am J Physiol Heart Circ Physiol (July 11, 2002). doi:10.1152/ajpheart.00150.2002
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Articles in PresS, published online ahead of print July 11, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00150.2002
Submitted on February 25, 2002
Accepted on July 8, 2002

{delta}-OPIOID RECEPTOR-INDUCED LATE PRECONDITIONING IS MEDIATED BY CYCLOOXYGENASE-2 IN CONSCIOUS RABBITS

Eitaro Kodani1, Yu-Ting Xuan1, Ken Shinmura1, Hitoshi Takano1, Xian-Liang Tang1, and Roberto Bolli1*

1 Cardiology, University of Louisville, Louisville, KY, USA

* To whom correspondence should be addressed. E-mail: rbolli{at}louisville.edu.

Although activation of {delta}-opioid receptors is known to induce both early and late preconditioning (PC) against myocardial infarction, the mechanisms for this salubrious effect are unclear. Furthermore, it is unknown whether {delta}-opioid receptors can also induce late PC against myocardial stunning. Using conscious rabbits (n=120), in this study we found that the {delta}-opioid receptor agonist BW373U86 induced late PC against myocardial stunning 24 h after treatment, and that this effect was abolished by the selective cyclooxygenase-2 (COX-2) inhibitors NS-398 and celecoxib. This protective effect was also abrogated by the selective {delta}1-opioid receptor antagonist BNTX, indicating that the {delta}1-opioid receptor is necessary for BW373U86-induced late PC. BW373U86 did not induce early PC against stunning. In addition, BW373U86 induced late PC against infarction, which was blocked by NS-398. At 24 h after BW373U86 administration, myocardial COX-2 protein expression and PGE2 and 6-keto-PGF1{alpha} levels were significantly increased. Taken together, these results demonstrate that activation of {delta}-opioid receptors induces late PC against both stunning and infarction via a COX-2-dependent mechanism.




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