Preconditioning of Isolated Rat Heart Is Mediated by Protein Kinase C

TLDR

Catecholamines are implicated in ischemic preconditioning. The study aimed to delineate the signal transduction pathways downstream of the α1‑adrenergic receptor in preconditioning. PKC antagonists block preconditioning, diacylglycerol infusion induces protection, and PKC‑δ translocation to the sarcolemma demonstrates that PKC is an effector of preconditioning in the isolated rat heart.

Abstract

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 α 1 -adrenergic receptor. The purpose of this study was to delineate the signal transduction of preconditioning distal to the α 1 -adrenergic receptor. Our results suggest that (1) transient ischemia and α 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 α 1 -adrenergic pathway, and (3) transient ischemia and α 1 -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.