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 reabsorption (J(HCO(3))) of surviving distal tubules, nephrectomized rats drank either water or a solution of Los, 7 days before microperfusion. J(HCO(3)) 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 J(HCO(3)), we perfused three inhibitors simultaneously [5-(N, N-dimethyl) amiloride hydrochloride, Conc, Schering 28080] with or without prior Los treatment: J(HCO(3)) was unchanged despite marked reduction of water reabsorption. We conclude enhanced distal tubule J(HCO(3)) of surviving nephrons is largely mediated by AT(1) receptor-dependent synthesis and insertion of apical H(+)-ATPase pumps in A-type intercalated cells.
Levine
D Z
DZ
Department of Medicine, Division of Nephrology, University of Ottawa and Ottawa Hospital, Ottawa, Ontario, Canada K1H 8M5.
Iacovitti
M
M
Luck
B
B
Hincke
M T
MT
Burns
K D
KD
Fryer
J N
JN
D000042:Absorption; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D019808:Losartan / Q000494:pharmacology*; D018942:Macrolides; D008297:Male; D008854:Microscopy, Electron; D009392:Nephrectomy; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
D057911:Angiotensin Receptor Antagonists; D000900:Anti-Bacterial Agents; D001639:Bicarbonates; D004791:Enzyme Inhibitors; D018942:Macrolides; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C036978:concanamycin A; D006180:Proton-Translocating ATPases; D019808:Losartan