ANG II-dependent HCO3- reabsorption in surviving rat distal tubules: expression/activation of H(+)-ATPase

Abstract

Distal tubules (DT) from sham or five-sixths nephrectomized (Nx) rats were perfused in vivo to evaluate the hypothesis that, after Nx, endogenous angiotensin II (ANG II) modulates DT in vivo bicarbonate reabsorption (JtCO2) via H(+)-adenosinetriphosphatase (H(+)-ATPase) and Na+/H+ exchange. In Nx rats JtCO2 was increased (65 +/- 7 vs. -24 +/- 21 pmol.min-1.mm-1, P < 0.01). Both luminal and intravenous AT1-receptor blockade by losartan reduced Nx DT JtCO2 (41 +/- 6 and 34 +/- 4 pmol.min-1.min-1, respectively, P < 0.05), whereas neither 10(-9) M nor 10(-11) M ANG II luminal perfusion increased JtCO2, suggesting preexisting high endogenous ANG II levels. The Na+/H+ antiporter inhibitors 5-(N-ethyl-N-isopropyl)-amiloride and 5-(N,N-dimethyl)-amiloride were without effect. Luminal perfusion of 5 nM concanamycin A, a V-type H(+)-ATPase inhibitor, reduced Nx DT JtCO2 (45 +/- 8 pmol.min-1.mm-1, P < 0.05). In Nx A-type intercalated cells, we demonstrated cellular hypertrophy, elaboration of apical microplicae, and enhanced expression/apical polarization of H(+)-ATPase. Thus ANG II is an important determinant in sustaining brisk DT JtCO2 following Nx and is associated with enhanced expression and A-type intercalated cell apical polarization of H(+)-ATPase.