Preconditioning of Isolated Rat Heart Is Mediated by Protein Kinase C

Abstract

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 α1-adrenergic receptor. The purpose of this study was to delineate the signal transduction of preconditioning distal to the α1-adrenergic receptor. Our results suggest that (1) transient ischemia and α1-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 α1-adrenergic pathway, and (3) transient ischemia and α1-adrenergic preconditioning are both characterized by similar translocation of PKC-δ to the sarcolemma of myocardium. These findings suggest that PKC is an effector of preconditioning in the isolated rat heart.