PKC activation with PMA in isolated rat hearts decreased PVA-independent VO2 by 28% and increased contractile efficiency by 41% (P<0.05), effects that were abolished by chelerythrine.
Does PKC activation with PMA alter myocardial O2 consumption and contractile efficiency in isolated rat hearts?
PKC activation by PMA decreases myocardial oxygen consumption and increases contractile efficiency in isolated rat hearts, effects that are reversed by PKC inhibition.
p-value: p=<0.05
The effect of protein kinase C (PKC) activation on cardiac mechanoenergetics 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 PKC inhibitor chelerythrine. Contractile efficiency was assessed as the reciprocal of the slope of the linear myocardial O2 consumption (VO2) pressure-volume area (PVA) relation. PMA decreased contractility (Emax; -30 +/- 8%; P < 0.05) and increased coronary perfusion pressure (+58 +/- 11%; P < 0.01) without altering left ventricular end-diastolic pressure. Concomitantly, PMA decreased PVA-independent VO2 nonmechanical energy expenditure for excitation-contraction (E-C) coupling and basal metabolism by 28 +/- 8% (P < 0.05) and markedly increased contractile efficiency (+41 +/- 8%; P < 0.05) in a manner independent of the coronary vascular resistance. Basal metabolism was not affected by PMA. Chelerythrine abolished the PMA-induced vasoconstriction, negative inotropy, decreased PVA-independent VO2, and increased contractile efficiency. We conclude that PKC-mediated phosphorylation of regulatory proteins reduces VO2 via effects on both the contractile machinery and the E-C coupling.
Noguchi et al. (Thu,) conducted a other in cardiac mechanoenergetics. Phorbol 12-myristate 13-acetate (PMA) with or without chelerythrine vs. Baseline/Control was evaluated on Contractile efficiency and PVA-independent VO2 (p=<0.05). PKC activation with PMA in isolated rat hearts decreased PVA-independent VO2 by 28% and increased contractile efficiency by 41% (P<0.05), effects that were abolished by chelerythrine.