Surviving rat distal tubule bicarbonate reabsorption: effects of chronic AT(1) blockade

To determine the in vivo effects of chronic ANG II type 1 (AT(1))-receptor blockade by losartan (Los) on enhanced unidirectional bicarbonate reabsorpt ion (J(HCO3)) of surviving distal tubules, nephrectomized rats drank either water or a solution of Los, 7 days before microperfusion. J(HCO3) was supp ressed by 50% after Los without further reduction by 5 nM concanamycin A (C onc), suggesting that Los suppresses all Conc-sensitive H+-ATPase pumping. Indeed, ultrastructural analysis of A-type intercalated cells revealed a 50 % reduction oT H+-ATPase immunogold labeling of the apical plasma membrane, whereas Western blotting showed that H+-ATPase protein levels were also re duced by one-half by Los treatment. To identify other transporters sustaini ng J(HCO3), We perfused three inhibitors simultaneously [5-(N,N-dimethyl) a miloride hydrochloride, Conc, Schering 28080] with or without prior Los tre atment: J(HCO3) was unchanged despite marked reduction of water reabsorptio n. We conclude enhanced distal tubule J(HCO3) of surviving nephrons is larg ely mediated by AT(1) receptor-dependent synthesis and insertion of apical H+-ATPase pumps in A-type intercalated cells.