REGULATION BY ANGIOTENSIN-II OF PHOSPHATE-TRANSPORT IN CARDIAC MYOCYTES

The purpose of this study was to test the hypothesis that angiotensin II (ang II) affects the transport of inorganic phosphate in adult ventricular myocytes. Ventricular myocytes were isolated from Dahl rats and allowed to take up P-32 inorganic phosphate (P-32-P(i)). The intracellular P-32 concentration increased rapidly and reached a peak at 5 min. Ang II, 10(-10) to 10(-5) M, produced a significant (P < 0.05) and concentration-dependent reduction in P-32-P(i) uptake that plateaued at 0.1 to 1.0-mu-M. Ang II at 1-mu-M produced a 30% reduction in V(max) and a slightly greater reduction in the Km of P-32-P(i) uptake, compared to myocytes that were not exposed to ang II. The ang II receptor antagonist saralasin (Sar1-Val5-Ala8-angiotensin II), significantly (P < 0.05) antagonized the action of ang II on P-32-P(i) uptake. TPA (12-O-tetradecanoylphorbol-13-acetate) also produced a significant (P < 0.05) reduction of P-32-P(i) uptake, suggesting that protein kinase C is involved in the transduction of ang II effects on intracellular P(i). P-32 Efflux from myocytes, pulsed with P-32-P(i) and chased with P(i)-free medium, was accentuated markedly by ang II; this effect was blunted by saralasin. These data suggest that ang II is capable of regulating total intracellular P(i) in the heart via two actions: (i) by inhibiting uptake of P(i) into the myocyte, and (ii) by increasing the efflux of phosphates out of the cell.