Pharmacologic Preconditioning Induced by β-Adrenergic Stimulation is Mediated by Activation of Protein Kinase C

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Abstract
Ischemic preconditioning (I-PC) occurs via activation of protein kinase C (PKC). This study was undertaken to determine whether pharmacologic preconditioning by β-adrenergic stimulation (β-PC) is mediated by PKC activation. Isolated rat hearts were subjected to 40-min ischemia and 30-min reperfusion. β-PC was induced by 0.25 μM isoproterenol pretreatment for 2 min followed by 10-min normoxic perfusion. β-PC enhanced the recovery of rate-pressure product of the ischemic/reperfused heart (79.1 ± 8.4% vs. 12.4 ± 1.6% of initial for Non-PC group, n = 6) and attenuated the release of creatine kinase during 30-min reperfusion (30.2 ± 2.2 vs. 59.8 ± 6.1 nmol/min/g wet wt for Non-PC group, n = 6), similar to an I-PC stimulus of 5-min ischemia and 5-min reperfusion. Treatment with 50 μM polymyxin B, a PKC inhibitor, abolished the cardioprotection of both β-PC and I-PC. Furthermore, similar changes in subcellular distribution of PKC were induced by both β-PC and I-PC. The changes in subcellular distribution of PKC-δ suggested its translocation from cytosol to membrane fraction, a marker of PKC activation. These results suggest that the cardioprotection induced by β-PC, like I-PC, is mediated by PKC activation.