The loop of Henle (LOH) reabsorbs approximately 15% of filtered HCO 3 - via a luminal Na+-H+ exchanger and H+ATPase. During acute metabolic alkalosis (AMA) induced by i.v. HCO 3 - infusion, we have observed previously inhibition of LOH net HCO 3 - reabsorption {Mathematical expression}, which contributes to urinary elimination of the HCO 3 - load and correction of the systemic alkalosis. To determine whether the activities of the Na+-H+ exchanger and/or H+-ATPase are reduced during AMA, two inhibitors believed to be sufficiently specific for each transporter were delivered by in vivo LOH microperfusion during AMA. AMA reduced LOH {Mathematical expression} from 205.0±0.8 to 96.2±11.8 pmol · min-1 (P<0.001). Luminal perfusion with bafilomycin A1 (10-4 mol · l-1) caused a further reduction in {Mathematical expression} by 83% and ethylisopropylamiloride (EIPA; 5.10-4 mol · l-1) completely abolished net HCO 3 - reabsorption. The combination of bafilomycin A1 and EIPA in the luminal perfusate was additive, resulting in net HCO 3 - secretion (-66.6±20.8 pmol · min-1;P<0.001) and abolished net fluid reabsorption (from 5.0±0.6 during AMA to 0.2±1.1 nl · min-1;P<0.001). To establish whether HCO 3 - secretion via luminal stilbenesensitive transport mechanism participates in LOH adaptation to AMA, we added diisothiocyanato-2,2′-stilbenedisulphonate (DIDS; 10-4 mol · l-1) to the perfusate. No effect was found. However, when the same LOH were exposed to luminal DIDS for more than 10 min, the direction of net HCO 3 - movement was reversed and net HCO 3 - secretion occurred: {Mathematical expression} changed from 90.6±8.8 to -91.9±34.1 pmol · min-1;P<0.01, an effect that was not observed in the control state (undisturbed acid-base balance). Thus, during AMA, neither the luminal Na+-H+ exchanger nor the H+-ATPase are noticeably suppressed. However, pharmacological elimination of both transporters, as well as prolonged exposure of the tubular lumen to DIDS, induced net HCO 3 - secretion. This secretory flux may reflect paracellular backflux due to the steeper blood to lumen HCO 3 - concentration gradient that presumably prevails in AMA. © 1994 Springer Verlag.
The effect of acute metabolic alkalosis on bicarbonate transport along the loop of Henle. The role of active transport processes and passive paracellular backflux
CAPASSO, Giovambattista;
1994
Abstract
The loop of Henle (LOH) reabsorbs approximately 15% of filtered HCO 3 - via a luminal Na+-H+ exchanger and H+ATPase. During acute metabolic alkalosis (AMA) induced by i.v. HCO 3 - infusion, we have observed previously inhibition of LOH net HCO 3 - reabsorption {Mathematical expression}, which contributes to urinary elimination of the HCO 3 - load and correction of the systemic alkalosis. To determine whether the activities of the Na+-H+ exchanger and/or H+-ATPase are reduced during AMA, two inhibitors believed to be sufficiently specific for each transporter were delivered by in vivo LOH microperfusion during AMA. AMA reduced LOH {Mathematical expression} from 205.0±0.8 to 96.2±11.8 pmol · min-1 (P<0.001). Luminal perfusion with bafilomycin A1 (10-4 mol · l-1) caused a further reduction in {Mathematical expression} by 83% and ethylisopropylamiloride (EIPA; 5.10-4 mol · l-1) completely abolished net HCO 3 - reabsorption. The combination of bafilomycin A1 and EIPA in the luminal perfusate was additive, resulting in net HCO 3 - secretion (-66.6±20.8 pmol · min-1;P<0.001) and abolished net fluid reabsorption (from 5.0±0.6 during AMA to 0.2±1.1 nl · min-1;P<0.001). To establish whether HCO 3 - secretion via luminal stilbenesensitive transport mechanism participates in LOH adaptation to AMA, we added diisothiocyanato-2,2′-stilbenedisulphonate (DIDS; 10-4 mol · l-1) to the perfusate. No effect was found. However, when the same LOH were exposed to luminal DIDS for more than 10 min, the direction of net HCO 3 - movement was reversed and net HCO 3 - secretion occurred: {Mathematical expression} changed from 90.6±8.8 to -91.9±34.1 pmol · min-1;P<0.01, an effect that was not observed in the control state (undisturbed acid-base balance). Thus, during AMA, neither the luminal Na+-H+ exchanger nor the H+-ATPase are noticeably suppressed. However, pharmacological elimination of both transporters, as well as prolonged exposure of the tubular lumen to DIDS, induced net HCO 3 - secretion. This secretory flux may reflect paracellular backflux due to the steeper blood to lumen HCO 3 - concentration gradient that presumably prevails in AMA. © 1994 Springer Verlag.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
