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 preconditioning by beta-adrenergic stimulation (beta-PC) is mediated by PKC activation. Isolated rat hearts were subjected to 40-min ischemia and 30-min reperfusion. Beta-PC was induced by 0.25 microM isoproterenol pretreatment for 2 min 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. 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 microM polymyxin B, a PKC inhibitor, abolished the cardioprotection of both beta-PC and I-PC. Furthermore, similar changes in subcellular distribution of PKC were induced by both beta-PC and I-PC. The changes in subcellular distribution of PKC-delta suggested its translocation from cytosol to membrane fraction, a marker of PKC activation. These results suggest that the cardioprotection induced by beta-PC, like I-PC, is mediated by PKC activation.
Yabe
K
K
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Ishishita
H
H
Tanonaka
K
K
Takeo
S
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011112:Polymyxin B / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D011493:Protein Kinase C; D003402:Creatine Kinase; D011112:Polymyxin B; D007545:Isoproterenol