Biphasic effect of angiotensin II on intracellular sodium concentration in rat proximal tubules.

Intracellular Na+ concentration ([Na+]i) was determined using ratiometric measurement of the Na(+)-sensitive fluorescent probe, sodium-binding benzofuran isophthalate (SBFI). Angiotensin II (ANG II, 10(-11)-10(-7) M), applied to the basolateral membrane of rat isolated proximal convoluted tubules, induced a rapid and reversible dose-dependent increase in [Na+]i, which was initiated within 300 ms. A maximal response was observed over the range 10(-9)-10(-7) M ANG II, with an average increase in [Na+]i of 7.4 +/- 1.0 mM. At higher concentrations (10(-6)-10(-5) M) ANG II decreased [Na+]i compared with control (14.2 +/- 0.6 mM). The increase in [Na+]i induced by 10(-9) M ANG II was attenuated by inhibiting the Na+/H+ antiporter with clonidine, whereas HOE-694, a specific blocker of the NHE-1 isoform of the Na+/H+ exchanger, had no effect. The increase in [Na+]i induced by 10(-9) M ANG II was enhanced by inhibition of the Na(+)-HCO3- cotransporter with hydrogen-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, with an average increase in [Na+]i of 17.1 +/- 6.6 mM. The data provide direct, high time resolution measurements of the effects of ANG II on [Na+]i in the proximal tubule and support the proposition that an increase in transepithelial Na+ reabsorption by ANG II involves stimulation of both an Na+/H+ exchanger and the Na(+)-HCO3- cotransporter.