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

Catecholamines have been implicated in the phenomenon of ischemic prec onditioning. We have previously demonstrated that ischemic preconditio ning against postischemic mechanical dysfunction in the isolated rat h eart is mediated by the alpha(1)-adrenergic receptor. The purpose of t his 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 precond itioning is inhibited by protein kinase C (PKC) antagonists, (2) funct ional protection against global ischemia/reperfusion injury can be ind uced by infusion of diacylglycerol, the second messenger of the alpha( 1)-adrenergic pathway, and (3) transient ischemia and alpha(1)-adrener gic preconditioning are both characterized by similar translocation of PKC-delta to the sarcolemma of myocardium. These findings suggest tha t PKC is an effector of preconditioning in the isolated rat heart.