Attenuation of heat shock-induced cardioprotection by treatment with the opiate receptor antagonist naloxone

Abstract

Attenuation of heat shock-induced cardioprotection by treatment with the opiate receptor antagonist naloxone. Am J Physiol Heart Circ Physiol 282: H2011-H2017, 2002. First published January 17, 2002 10.1152/ajpheart.00828.2001.-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°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 Ϯ 3 vs. 58 Ϯ 4%, P Ͻ 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 Ϯ 6 vs. 16 Ϯ 3%, P Ͻ 0.001). Acute treatment with naloxone (3 mg/kg) 48 h after recovery from HS also significantly attenuated the delayed protective effect (47 Ϯ 4 vs. 16 Ϯ 3%, P Ͻ 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.heat shock proteins; whole body hyperthermia

Failure to confer cardioprotection and to increase the expression of heat-shock protein 70 by preconditioning with a ?-opioid receptor agonist during ischaemia and reperfusion in streptozotocin-induced diabetic rats

“…We found that the myocardial infarct caused by ischaemia and reperfusion was significantly greater in diabetic than in nornist, attenuates both the cardioprotective effect and increased expression of HSPs [15].…”

The influence of extremely low frequency magnetic fields on cytoprotection and repair

“…Furthermore, opioids may protect against damage if administered during the window of opportunity after ischemia sets in but prior to reperfusion [Chang et al, 2005]. Blocking opioid receptors with naloxone (a general opioid antagonist) also attenuated the protective effect of heat stress preconditioning in a study [Patel et al, 2002], further supporting the role opioids may play in ischemia-reperfusion protection. Note that the different opioid receptor subtypes appear to have different functions in this regard.…”

Exercise improves postischemic function in aging hearts

“…18, 30, and 31). However, there is also evidence that its increased expression is not required for improved myocardial tolerance to I/R in young rats after one to three bouts of exercise (13,34) and that increased expression of HSP70 after heat shock does not necessarily result in cardioprotection (16,28,37). Whereas HSP70 could have played a major role in exercise-induced cardioprotection in the youngest group, this is unlikely to be the case in the older groups because the expression of the chaperone was only modestly elevated after exercise.…”