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 (J(sec)) and reabsorptive flux (J(reab))] of distal t ubule bicarbonate reabsorption and to test the hypothesis that Jreah i s dependent on bafilomycin A(1)-sensitive H+-adenosinetriphosphatase a ctivity. During 18 h of severe acidosis there was a significant decrea se in J(sec) (-15 +/- 3 vs. -38 +/- 5 pmol min(-1).mm(-1), P < 0.05) a nd a significant increase in J(reab) (37 +/- 6 vs. 0 +/- 5 pmol.min(-1 ).mm(-1), P < 0.05), which was insensitive to 10(-5) M bafilomycin A(1 ), 10(-5) M Sch-28080, and 3 mM amiloride. After 3 days of acid loadin g, these same inhibitors reduced J(reab) by similar to 60%. However, w hen water flux was completely inhibited by isosmotic perfusion, a sign ificant J(reab) (15 +/- 2 pmol.min(-1).mm(-1)) resistant to 10(-5) M b afilomycin Al persisted, as in severe acidosis. In reabsorbing distal tubules of overnight-fasted rats, Sch-28080 elicited no inhibition, wh ereas bafilomycin Al and amiloride had significant effects (28 +/- 5, 24 +/- 4, respectively, vs. 50 +/- 4 pmol.min(-1).mm(-1) for fasted ra ts, P < 0.05). Thus, although J(sec) is reduced in the transition from mild to severe metabolic acidosis of 18-h duration, the predominant e ffect is a stimulation of bafilomycin A(1)-resistant J(reab).