Activation of PKC decreases myocardial O-2 consumption and increases contractile efficiency in rats

The effect of protein kinase C (PKC) activation on cardiac mechanoenergetic s is not fully understood. To address this issue, we determined the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) on isolated rat hearts. Hearts were exposed to PMA with or without pretreatment with the P KC inhibitor chelerythrine. Contractile efficiency was assessed as the reci procal of the slope of the linear myocardial O-2 consumption ((V)over dotO( 2)) pressure-volume area (PVA) relation. PMA decreased contractility (E-max ; -30 +/-8%; P<0.05) and increased coronary perfusion pressure (+58<plus/mi nus>11%; P<0.01) without altering left ventricular end-diastolic pressure. Concomitantly, PMA decreased PVA-independent (V)over dotO(2) [nonmechanical energy expenditure for excitation-contraction (E-C) coupling and basal met abolism] by 28<plus/minus>8% (P<0.05) and markedly increased contractile ef ficiency (+41<plus/minus>8%; P<0.05) in a manner independent of the coronar y vascular resistance. Basal metabolism was not affected by PMA. Chelerythr ine abolished the PMA-induced vasoconstriction, negative inotropy, decrease d PVA-independent (V)over dotO(2), and increased contractile efficiency. We conclude that PKC-mediated phosphorylation of regulatory proteins reduces (V)over dotO(2) via effects on both the contractile machinery and the E-C c oupling.