Angiotensin II stimulation of Na(+)-H+ exchange in proximal tubule cells

Experiments were performed to evaluate the effect of angiotensin II (ANG II) on the sodium transport activity of isolated intact rabbit proximal tubule cells. Initial rates of 22Na(+) uptake were measured in Na+-depleted and ouabain-treated cells in the presence of an opposing H+ gradient (pHin less than pHout). ANG II (10(-12)-10(-9) M) stimulated the initial rate of 22Na+ uptake by 33 +/- 2%, whereas amiloride (0.5 mM) inhibited both basal and ANG II-stimulated 22Na+ uptake. ANG II-stimulated rate of 22Na+ uptake was inhibited by the receptor antagonist saralasin. Additional experiments were performed to evaluate the effect of ANG II on the rate of recovery of pHin in acid-loaded proximal tubule cells. Cells were acid loaded by an NH4Cl pulse in the presence of the pH-sensitive fluorescent dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. ANG II increased the initial rate of intracellular alkalinization, and this effect was inhibited by amiloride (1.0 mM). ANG II stimulation increased the Vmax of H+ efflux (from 0.53 +/- 0.02 to 0.64 +/- 0.04 pH units/min) without changing the Km for extracellular Na+. The present findings indicate that physiological concentrations of ANG II stimulate an amiloride-sensitive Na+-H+ antiport in proximal tubule cells.