Influence of Sodium Balance on the Ability of Diuretics to Inhibit Tubular Reabsorption

Abstract

Chlorothiazide and ethacrynic acid were given to normal humans and patients with cirrhosis and ascites, with replacement of urinary losses, to obtain information on (1) the influence of different states of sodium balance and excretion on the effectiveness of the drugs in blocking tubular reabsorption and promoting excretion of sodium, and (2) the influence of different states of sodium balance on reabsorption of sodium by different segments of the nephron of man. The results demonstrated that in normal man the natriuretic response to these agents is markedly influenced by the existing state of sodium balance. The differences in response to the drugs related both to differences in the filtered load of sodium and to differences in the fraction of filtered sodium reabsorbed at the diuretic-sensitive distal tubular sites. Sodium loading in the presence of a mineralocorticoid was associated with a thiazideinduced increment in the excretion of sodium which was 10 times greater than that observed during sodium depletion. This effect is suggestive of decreased proximal tubular reabsorption. In patients with cirrhosis and sodium retention the fraction of filtered sodium reabsorbed at both diuretic-sensitive tubular sites was diminished, suggesting increased proximal tubular reabsorption. In addition to demonstrating a striking influence of sodium balance on the natriuretic response to the diuretics, the results suggest that in man sodium diuresis is associated with decreased fractional reabsorption by the proximal tubule and increased fractional and absolute sodium reabsorption by the distal tubule. In patients accumulating edema and ascites, an increase in the fractional reabsorption of sodium appears to occur in the proximal tubule and could account for limited effectiveness of the diuretic agents.