Pharmacologic preconditioning induced by beta-adrenergic stimulation is mediated by activation of protein kinase C

Ischemic preconditioning (I-PC) occurs via activation of protein kinase C ( PKC). This study was undertaken to determine whether pharmacologic precondi tioning by beta-adrenergic stimulation (beta-PC) is mediated by PKC activat ion. Isolated rat hearts were subjected to 40-min ischemia and 30-min reper fusion. beta-PC was induced by 0.25 mu M isoproterenol pretreatment for 2 m in followed by 10-min normoxic perfusion. beta-PC enhanced the recovery of rate-pressure product of the ischemic/reperfused heart (79.1 +/- 8.4% vs. 1 2.4 +/- 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 o f 5-min ischemia and 5-min reperfusion. Treatment with 50 mu M polymyxin B, a PKC inhibitor, abolished the cardioprotection of both beta-PC and I-PC. Furthermore, similar changes in subcellular distribution of PKC were induce d by both beta-PC and I-PC. The changes in subcellular distribution of PKC- delta suggested its translocation from cytosol to membrane fraction, a mark er of PKC activation. These results suggest that the cardioprotection induc ed by beta-PC, like I-PC, is mediated by PKC activation.