LEVINE, DAVID Z., IACOVITTI, MICHELLE, LUCK, BRIAN, HINCKE, MAXWELL T., BURNS, KEVIN D., and FRYER, JAMES N.
Levine, David Z., Michelle Iacovitti, Brian Luck, Maxwell T. Hincke, Kevin D. Burns, and James N. Fryer. Surviving rat distal tubule bicarbonate reabsorption: effects of chronic [AT.sub.1] blockade. Am. J. Physiol. Renal Physiol. 278: F476-F483, 2000.--To determine the in vivo effects of chronic ANG II type 1 ([AT.sub.1])-receptor blockade by losartan (Los) on enhanced unidirectional bicarbonate reabsorption ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]) of surviving distal tubules, nephrectomized rats drank either water or a solution of Los, 7 days before microperfusion. [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] was suppressed by 50% after Los without further reduction by 5 nM concanamycin A (Conc), suggesting that Los suppresses all Conc-sensitive [H.sup.+]-ATPase pumping. Indeed, ultrastructural analysis of A-type intercalated cells revealed a 50% reduction of [H.sup.+]-ATPase immunogold labeling of the apical plasma membrane, whereas Western blotting showed that [H.sup.+]-ATPase protein levels were also reduced by one-half by Los treatment. To identify other transporters sustaining [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII], we perfused three inhibitors simultaneously [5-(N,N,-dimethyl) amiloride hydrochloride, Conc, Schering 28080] with or without prior Los treatment: [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] was unchanged despite marked reduction of water reabsorption. We conclude enhanced distal tubule [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] of surviving nephrons is largely mediated by [AT.sub.1] receptor-dependent synthesis and insertion of apical [H.sup.+]-ATPase pumps in A-type intercalated cells. kidney failure; receptors; losartan; proton-transporting adenosine 5'-triphosphate synthase; concanamycin A