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Micropuncture studies have disclosed that extracellular fluid (ECF) volume expansion inhibits sodium reabsorption in the proximal tubule. The diuresis that ensues represents only a portion of the increment in sodium and water escaping proximal reabsorption, since a large and variable fraction of the increment is reabsorbed distally. In certain experimental models proximal reabsorption may be depressed by ECF volume expansion, yet only a negligible amount of sodium appears in the final urine. This suggests that saline diuresis is the consequence of depressed distal sodium reabsorption. Previous clearance and micropuncture studies have not conclusively proven this. Eight dogs were studied repeatedly: in some studies glomerular filtration rate and distal delivery were increased markedly without sodium administration; in others comparably high distal sodium loads were achieved by progressive 1/2 isotonic saline infusion. C(H2O) at high distal sodium loads was depressed by expansion of the ECF volume with hypotonic saline. The difference in free water formation between dogs which did and did not receive hypotonic saline was accounted for by the difference in sodium excretion. In one dog hypotonic saline expansion failed to depress free water formation; likewise the level of natriuresis in this dog was severely attenuated. The results of these experiments provide strong evidence that the natriuresis that occurs following ECF volume expansion with saline is a consequence of alteration in function of the distal nephron.

Effect of Extracellular Volume Expansion upon Sodium Reabsorption in the Distal Nephron of Dogs