Attenuation of heat shock-induced cardioprotection by treatment with the opiate receptor antagonist naloxone.
Whole body hyperthermia induces heat shock proteins (HSPs), which confer cardioprotection. Several opioid receptor subtypes are expressed in the heart and are linked to cardioprotection; however, no one has attempted to link the protection elicited by heat stress (HS) to opioids. Therefore, we investigated the effect of an opiate receptor antagonist, naloxone, on HS-induced cardioprotection. Anesthetized Sprague-Dawley rats were subjected to HS (42 degrees C for 20 min) with and without naloxone pretreatment and were allowed to recover for 48 h. They then underwent 30 min of ischemia followed by 2 h of reperfusion. An acute HS group was given an intravenous bolus of naloxone (3 mg/kg) 10 min before index ischemia. Infarct size (IS), expressed as a percentage of the area at risk (IS/AAR), was determined. The right heart was excised for analysis of HSP content by Western blot. Heat-shocked rats showed significant reductions in IS/AAR versus control (16 +/- 3 vs. 58 +/- 4%, P < 0.001). Pretreatment with naloxone before HS attenuated the protective effects in a dose-dependent fashion, with significant attenuation of protection occurring at 15 mg/kg naloxone versus heat shock (42 +/- 6 vs. 16 +/- 3%, P < 0.001). Acute treatment with naloxone (3 mg/kg) 48 h after recovery from HS also significantly attenuated the delayed protective effect (47 +/- 4 vs. 16 +/- 3%, P < 0.001). No difference was seen in the level of HSP70 induced in the different groups. We conclude that heat shock-induced cardioprotection can be attenuated by naloxone, an opiate receptor antagonist, without reducing the levels of certain HSPs. These results suggest there may be a link between the endogenous release of opioids and HS that mediates cardioprotection.
Patel
Hemal H
HH
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Hsu
Anna
A
Gross
Garrett J
GJ
D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D006339:Heart Rate; D006360:Heat-Shock Proteins / Q000032:analysis / Q000502:physiology*; D006439:Hemodynamics; D006358:Hot Temperature; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000737:chemistry; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology
D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone