ANG-II-DEPENDENT HCO3(-) REABSORPTION IN SURVIVING RAT DISTAL TUBULES- EXPRESSION ACTIVATION OF H+-ATPASE/

Distal tubules (DT) from sham or five-sixths nephrectomized (Nx) rats were perfused in vivo to evaluate the hypothesis that, after Nx, endog enous angiotensin II (ANG II) modulates DT in vivo bicarbonate reabsor ption (J(tCO2)) via H+-adenosinetriphosphatase (H+-ATPase) and Na+/Hexchange. In Nx rats J(tCO2) was increased (65 +/- 7 vs. -24 +/- 21 pm ol.min(-1).mm(-1), P < 0.01). Both luminal and intravenous ATI-recepto r blockade by losartan reduced Nx DT J(tCO2) (41 +/- 6 and 34 +/- 4 pm ol.min(-1).mm(-1), respectively, P < 0.05), whereas neither 10(-9) M n or 10(-11) M ANG II luminal perfusion increased J(tCO2) suggesting pre existing high endogenous ANG II levels. The Na+/H+ antiporter inhibito rs 5-(N-ethyl-N-isopropyl) amiloride and 5-(N,N-dimethyl)-amiloride we re without effect. Luminal perfusion of 5 nM concanamycin A, a V-type H+-ATPase inhibitor, reduced Nx DT J(tCO2), (45 +/- 8 pmol.min(-1).mm( -1), P < 0.05). In Nx A-type intercalated cells, we demonstrated cellu lar hypertrophy, elaboration of apical microplicae, and enhanced expre ssion/apical polarization of H+-ATPase. Thus ANG II is an important de terminant in sustaining brisk DT J(tCO2) following Nx and is associate d with enhanced expression and A-type intercalated cell apical polariz ation of H+-ATPase.