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Am J Physiol Heart Circ Physiol 283: H1943-H1957, 2002. First published July 11, 2002; doi:10.1152/ajpheart.00150.2002
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Vol. 283, Issue 5, H1943-H1957, November 2002

delta -Opioid receptor-induced late preconditioning is mediated by cyclooxygenase-2 in conscious rabbits

Eitaro Kodani, Yu-Ting Xuan, Ken Shinmura, Hitoshi Takano, Xian-Liang Tang, and Roberto Bolli

Experimental Research Laboratory, Division of Cardiology, University of Louisville and Jewish Heart and Lung Institute, Louisville, Kentucky 40292

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. By using conscious rabbits (n = 120) in this study, we found that the delta -opioid receptor agonist (±)-4-{(alpha -R*)-alpha -[(2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxybenzyl}-N,N-diethylbenzamide (BW-373U86) induced late PC against myocardial stunning 24 h after treatment and that this effect was abolished by the selective cyclooxygenase-2 (COX-2) inhibitors N-[2-(cyclohexyloxy)4-nitrophenyl]methanesulfonamide (NS-398) and celecoxib. This protective effect was also abrogated by the selective delta 1-opioid receptor antagonist 7-benzylidenenaltrexone, indicating that the delta 1-opioid receptor is necessary for BW-373U86-induced late PC. BW-373U86 did not induce early PC against stunning. In addition, BW-373U86 induced late PC against infarction, which was blocked by NS-398. At 24 h after BW-373U86 administration, myocardial COX-2 protein expression and PGE2 and 6-keto-PGF1alpha levels were significantly increased. These results demonstrate that activation of delta -opioid receptors induces late PC against both stunning and infarction via a COX-2-dependent mechanism.

ischemic-reperfused; BW-373U86; 7-benzylidenenaltrexone


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