The cellular sodium transport pool and sodium transepithelial fluxes were investigated in vivo in rat distal colon in relation to sodium loading by intravenous infusion (3·5 h), and to short (4 h) and prolonged (72 h) i.v. administration of aldosterone. Considerable natriuresis and increase in body sodium content were produced by the sodium load but there was no significant effect on the transcellular sodium flux (active absorption from lumen to plasma) or on the sodium transport pool. Both short and prolonged aldosteronism produced similar increases in the transport pool and in the transcellular sodium flux, but the transepithelial electrical potential difference (p.d.) was significantly greater in rats given the prolonged infusion. Addition of amiloride to the solution in the lumen of the colon almost completely abolished the p.d., the transport pool and the transcellular sodium flux of the rats receiving prolonged infusion, but had much less effect in those given the short infusion. The time-course of recovery of p.d. following prolonged aldosteronism was similar to that described for the turnover rate of rat colonic epithelial cells.
Lithium within the lumen had no significant effect in untreated rats but after prolonged aldosterone infusion lithium reduced the p.d. and the transcellular sodium flux although the transport pool was not reduced. These findings are consistent with the hypothesis that aldosteronism renders the apical membranes of the epithelial cells permeable to lithium and that intracellular accumulation of lithium depresses active sodium transfer.
The observations are interpreted in terms of an epithelial model in which aldosterone induces amiloride-sensitive pathways (diffusion channels permeable to sodium and lithium) in the apical membrane which totally replace the amiloride-insensitive pathways when aldosteronism is prolonged; the resulting expansion of the sodium transport pool is the stimulus for increased active sodium transport across the basolateral membranes.