Effects of Atrial Natriuretic Factor on Angiotensin-IIand Phorbol Ester-Stimulated Protein Kinase-C and Prostacyclin Production in Cultured Rat Aortic Smooth Muscle Cells*

The vasoconstrictor hormone angiotensin-II (AII) raises cytosolic free calcium and stimulates protein kinase-C (PKC) activity in vascular smooth muscle cells (VSMC). Phorbol-12-myristate-13-acetate (PMA) directly activates PKC in these cells. Both of these agonists stimulate prostacyclin production. Several studies have shown that atrial natriuretic factor (ANF) does not interfere with the AII-induced early calcium response. We, therefore, examined the effects of ANF on PKC activity and prostacyclin production in cultured rat aortic VSMC. PKC activity was determined in the membranous and cytosolic fractions after anion exchange chromatography. ANF (10(-7) M) inhibited by 44 +/- 3% and 39 +/- 8% the increase in membranous PKC activity induced by AII and PMA, respectively. ANF (10(-7) M) inhibited PMA-stimulated prostacyclin production, whereas AII-induced prostacyclin production remained unaffected. Thus, our results suggest that some biological effects induced by ANF in VSMC are mediated by an inhibition of membranous PKC activity.