Wong. Inducible HSP70 mediates delayed cardioprotection by U-50488H pretreatment in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 281: H40-H47, 2001.-To test the hypothesis that heat-shock proteins (HSPs) mediate delayed cardioprotection of prior -opioid receptor (-OR) stimulation, we first correlated cellular injury and viability with the expression of HSP70s in isolated rat ventricular myocytes subjected to prior -OR stimulation with the selective agonist ) and delayed lethal

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... ated ischemia (LSI). Cell injury and viability were indicated by lactate dehydrogenase release and trypan blue exclusion, respectively. The reduced injury and increased viability after pretreatment with U-50488H were concentration dependent and correlated directly with the expression of both stress-inducible (HSP70) and constitutive (HSC70) proteins. The effects mimic those with metabolic inhibition preconditioning (MIP). The cardioprotection against LSI by pretreatment with U-50488H and MIP was abolished and antagonized, respectively, via blockade of the -OR by its selective antagonist, nor-binaltorphimine. We also found that blockade of the production of HSP70 but not HSC70 blocked the inhibitory effect of pretreatment with U-50488H on injury and viability. These observations provide evidence that stress-inducible HSP70 mediates delayed cardioprotection of prior -OR stimulation. -opioid receptor; metabolic inhibition; preconditioning; heat shock protein 70; cellular injury