In vivo adaptation of bicarbonate reabsorption by rat distal tubules during acid loading.
We carried out in vivo microperfusion experiments in acid-loaded rats to characterize the adaptive response of the unidirectional components secretory flux (Jsec) and reabsorptive flux (Jreab)] of distal tubule bicarbonate reabsorption and to test the hypothesis that Jreab is dependent on bafilomycin A1-sensitive H(+)-adenosinetriphosphatase activity. During 18 h of severe acidosis there was a significant decrease in Jsec (-15 +/- 3 vs. -38 +/- 5 pmol.min-1.mm-1, P < 0.05) and a significant increase in Jreab (37 +/- 6 vs. 0 +/- 5 pmol.min-1.mm-1, P < 0.05), which was insensitive to 10(-5) M bafilomycin A1, 10(-5) M Sch-28080, and 3 mM amiloride. After 3 days of acid loading, these same inhibitors reduced Jreab by approximately 60%. However, when water flux was completely inhibited by isosmotic perfusion, a significant Jreab (15 +/- 2 pmol.min-1.mm-1) resistant to 10(-5) M bafilomycin A1 persisted, as in severe acidosis. In reabsorbing distal tubules of overnight-fasted rats, Sch-28080 elicited no inhibition, whereas bafilomycin A1 and amiloride had significant effects (28 +/- 5, 24 +/- 4, respectively, vs. 50 +/- 4 pmol.min-1.mm-1 for fasted rats, P < 0.05). Thus, although Jsec is reduced in the transition from mild to severe metabolic acidosis of 18-h duration, the predominant effect is a stimulation of bafilomycin A1-resistant Jreab.
Department of Medicine, University of Ottawa, Ontario, Canada.
D Z
DZ
Levine
M
M
Iacovitti
S
S
Buckman
D
D
Vandorpe
V
V
Harrison
D M
DM
Boisvert
S P
SP
Nadler
D000064:Acclimatization; D000138:Acidosis / Q000503:physiopathology*; D000208:Acute Disease; D000584:Amiloride / Q000494:pharmacology; D000643:Ammonium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D002908:Chronic Disease; D004032:Diet; D005215:Fasting; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology*; D018942:Macrolides; D008297:Male; D010477:Perfusion / Q000379:methods; D006180:Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D000935:Antifungal Agents; D001639:Bicarbonates; D007093:Imidazoles; D018942:Macrolides; C035235:Sch 28080; D000643:Ammonium Chloride; D000584:Amiloride; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases; D006851:Hydrochloric Acid