Aldosterone rapidly represses protein kinase C activity in neonatal rat cardiomyocytes in vitro.

Aldosterone lowers protein kinase C (PKC) activity in myocyte-enriched cultures from neonatal Sprague-Dawley rat hearts, with activity measured by the transfer of phosphate to myristolated alanine-rich C-kinase substrate, in the presence of Ca2+, phosphatidylserine, and diolein. The effect is rapid, with a significant effect after 1 min exposure, half maximal at < or = 1 nM aldosterone, with steroids showing a hierarchy of potency aldosterone = 9alpha fluorocortisol > deoxycorticosterone > corticosterone > spironolactone. Both Ca2+-dependent and -independent PKC activity appear equally inhibited by aldosterone, and PMA-stimulated increases in PKC activity appear similarly aldosterone-sensitive. No displaceable binding of [3H]aldosterone to purified PKC can be shown, evidence against a direct effect of aldosterone on PKC; aldosterone does not alter basal or PMA-stimulated PKC activity in cardiac fibroblasts, evidence for a cell-specific mediator of the myocyte effect. Taken with the previous demonstration of the potentiation of aldosterone-specific MR-mediated effects by PKC activation, the present data argue for the existence of a complex cross-talk mechanism between aldosterone and factors affecting PKC activity in the heart.