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Am J Physiol Renal Physiol 278: F476-F483, 2000;
0363-6127/00 $5.00
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Vol. 278, Issue 3, F476-F483, March 2000

Surviving rat distal tubule bicarbonate reabsorption: effects of chronic AT1 blockade

David Z. Levine1, Michelle Iacovitti1, Brian Luck2, Maxwell T. Hincke2, Kevin D. Burns1
James N. Fryer2
(With the Technical Assistance of A. Slater)

Departments of 1 Medicine and 2 Cellular and Molecular Medicine, Division of Nephrology, University of Ottawa and Ottawa Hospital, Ottawa, Ontario, Canada K1H 8M5

To determine the in vivo effects of chronic ANG II type 1 (AT1)-receptor blockade by losartan (Los) on enhanced unidirectional bicarbonate reabsorption (JHCO3) of surviving distal tubules, nephrectomized rats drank either water or a solution of Los, 7 days before microperfusion. JHCO3 was suppressed by 50% after Los without further reduction by 5 nM concanamycin A (Conc), suggesting that Los suppresses all Conc-sensitive H+-ATPase pumping. Indeed, ultrastructural analysis of A-type intercalated cells revealed a 50% reduction of H+-ATPase immunogold labeling of the apical plasma membrane, whereas Western blotting showed that H+-ATPase protein levels were also reduced by one-half by Los treatment. To identify other transporters sustaining JHCO3, we perfused three inhibitors simultaneously [5-(N,N-dimethyl) amiloride hydrochloride, Conc, Schering 28080] with or without prior Los treatment: JHCO3 was unchanged despite marked reduction of water reabsorption. We conclude enhanced distal tubule JHCO3 of surviving nephrons is largely mediated by AT1 receptor-dependent synthesis and insertion of apical H+-ATPase pumps in A-type intercalated cells.

kidney failure; receptors; losartan; proton-transporting adenosine 5'-triphosphate synthase; concanamycin A


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