Gender and aging do not impair opioid-induced late preconditioning in rats.
Opioids have been shown to confer late preconditioning against ischemia/reperfusion injury in several species. However, it is unknown whether gender or aging affects opioid-induced cardioprotection. Isolated perfused hearts from Fischer 344 rats were subjected to 20 min of global ischemia followed by 20 min of reperfusion. BW373U86, a delta-opioid receptor agonist, was administered s.c. at varying doses (0.1, 0.33, 1.0 mg/kg) 24 h before (BW0.1, BW0.33 and BW1.0, respectively). In 12-week-old male (YM) rats, the recovery of LV developed pressure (LVDP) after ischemia/reperfusion improved significantly in BW0.33 and BW1.0, compared with the control (C). In 78-week-old male (OM) rats, the recovery of LV function after ischemia/reperfusion improved and the total release of CK and LDH during reperfusion was attenuated in BW1.0. In 12-week-old female (YF) rats, the recovery of LV function improved only in BW0.33 but not in BW0.1 and BW1.0. The cardioprotective effect afforded by BW373U86 was completely abolished by NS-398, a COX-2 selective inhibitor, in YM, YF, and OM, although NS-398 in itself did not affect myocardial ischemia/reperfusion injury. The levels of 6-keto-PGF(1alpha) (a stable metabolite of PGI(2)) in coronary effluent during reperfusion were higher in the BW373U86-pretreated group that showed cardioprotection than in C and this increase in PGI(2) production was also inhibited by NS-398 in YM, YF, and OM. In conclusion, BW373U86-induced late preconditioning can be observed in aged and female hearts. A COX-2-dependent increase in PGI(2) production is essential for BW373U86-induced late PC in both sexes and in both young and old rats.
Shinmura
Ken
K
Division of Geriatric Medicine, Dept. of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku Tokyo 160-8582, Japan. shimmura@sc.itc.keio.ac.jp
Nagai
Maiko
M
Tamaki
Kayoko
K
Bolli
Roberto
R
D000375:Aging / Q000502:physiology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D051546:Cyclooxygenase 2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009294:Narcotics / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D012727:Sex Characteristics
D001549:Benzamides; D002316:Cardiotonic Agents; D007527:Isoenzymes; D009294:Narcotics; D010879:Piperazines; D011453:Prostaglandins; C083877:BW 373U86; D003577:Cytochrome P-450 Enzyme System; D007770:L-Lactate Dehydrogenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003402:Creatine Kinase; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase