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The separate effects of volume expansion and of increased delivery of sodium on sodium reabsorption in the diluting segment of the distal nephron were studied in man. In six normal subjects during a sustained water diuresis, sodium delivery to the distal nephron was increased without volume expansion by the administration of acetazolamide. In these subjects, free water clearance rose linearly as a function of urine flow. In five patients with complete, central diabetes insipidus, distal sodium delivery was increased by the infusion of hypertonic saline during a sustained water diuresis. In four of these five patients, changes in free water clearance were also observed during hypertonic saline diuresis in the presence of distal blockade of sodium reabsorption with chlorothiazide. At high rates of distal delivery the following observations were made: (a) free water clearance was lower and fractional sodium excretion higher during saline diuresis compared to acetazolamide diuresis; (b) although free water clearance was moderately reduced by chlorothiazide at low rates of urine flow, there was no difference in free water clearance between saline loading alone and saline plus chlorothiazide at high rates of urine flow; and (c) during saline loading free water clearance rose without evidence of a limit when increased distal delivery was accompanied by spontaneous increases in glomerular filtration rate, but tended toward a limit when glomerular filtration rate remained constant. The data indicate that during acute volume expansion with saline, there is a decrease in the fraction of delivered sodium reabsorbed in the distal nephron when compared to the response of the distal nephron to comparable increases in distal sodium delivery in the absence of volume expansion.

Effects of increased sodium delivery on distal tubular sodium reabsorption with and without volume expansion in man