Atrial natriuretic peptides inhibit protein kinase C activation in rat aortic smooth muscle

The effects of synthetic atrial natriuretic peptide and a cyclic guanosine 3',5'-monophosphate analogue, 8-bromo cGMP, on protein kinase C activation in rat aortic smooth muscle from spontaneously hypertensive and control Wistar-Kyoto rats were examined. Both atrial natriuretic peptide and 8-bromo cGMP inhibited protein kinase C activation by phenylephrine, an alpha 1-adrenoceptor agonist. When phorbol 12,13-dibutyrate was used, a substance which bypasses phospholipase C activation and directly activates protein kinase C, only atrial natriuretic peptide was effective in inhibiting activation. Additionally, it was found that spontaneously hypertensive rat aorta showed significantly greater basal and stimulated levels of protein kinase C in comparison with Wistar-Kyoto rat aorta. The results suggest first, a defective protein kinase C system in hypertensive rats and that atrial natriuretic peptide attenuates protein kinase C activation through cGMP-dependent and cGMP-independent mechanisms. This inhibition of protein kinase C activity may then lead to vasorelaxation.