PRECONDITIONING OF ISOLATED RAT-HEART IS MEDIATED BY PROTEIN-KINASE-C

Catecholamines have been implicated in the phenomenon of ischemic preconditioning. We have previously demonstrated that ischemic preconditioning against postischemic mechanical dysfunction in the isolated rat heart is mediated by the alpha(1)-adrenergic receptor. The purpose of this study was to delineate the signal transduction of preconditioning distal to the alpha(1)-adrenergic receptor. Our results suggest that (1) transient ischemia and alpha(1)-adrenergic receptor-induced preconditioning is inhibited by protein kinase C (PKC) antagonists, (2) functional protection against global ischemia/reperfusion injury can be induced by infusion of diacylglycerol, the second messenger of the alpha(1)-adrenergic pathway, and (3) transient ischemia and alpha(1)-adrenergic preconditioning are both characterized by similar translocation of PKC-delta to the sarcolemma of myocardium. These findings suggest that PKC is an effector of preconditioning in the isolated rat heart.