| Abstract | 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. |
| Authors | Hemal H Patel, Anna Hsu, Garrett J Gross
(Affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.)
|
| Journal | American journal of physiology. Heart and circulatory physiology
(Am J Physiol Heart Circ Physiol)
Vol. 282
Issue 6
Pg. H2011-7
(Jun 2002)
ISSN: 0363-6135 United States |
| PMID | 12003805
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- HSP70 Heat-Shock Proteins
- Heat-Shock Proteins
- Narcotic Antagonists
- Receptors, Opioid
- Naloxone
|
| Topics |
- Animals
- Blood Pressure
- Blotting, Western
- HSP70 Heat-Shock Proteins
(analysis)
- Heart Rate
- Heat-Shock Proteins
(analysis, physiology)
- Hemodynamics
- Hot Temperature
- Male
- Myocardial Reperfusion Injury
(prevention & control)
- Myocardium
(chemistry)
- Naloxone
(pharmacology)
- Narcotic Antagonists
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Opioid
(antagonists & inhibitors, physiology)
|
