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, 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.
Levine
D Z
DZ
Department of Medicine, University of Ottawa, Ontario, Canada.
Iacovitti
M
M
Buckman
S
S
Hincke
M T
MT
Luck
B
B
Fryer
J N
JN
D000042:Absorption; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D015153:Blotting, Western; D007150:Immunohistochemistry; D007686:Kidney Tubules, Distal / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009392:Nephrectomy / Q000379:methods; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D000804:Angiotensin II; D006180:Proton-Translocating ATPases