Demonstration of a hormonal inhibitor of proximal tubular reabsorption during expansion of extracellular volume with isotonic saline.

Evidence for the elaboration of a hormonal inhibitor of renal tubular reabsorption in response to expansion of extracellular fluid volume was obtained by examining the effects of plasma from rats and dogs undergoing saline diuresis on the rate of proximal tubular reabsorption measured both directly by micropuncture techniques and indirectly by clearance techniques. Intravenous infusion of plasma from salineloaded rats and dogs, but not plasma from control animals, inhibited the intrinsic reabsorptive capacity of the proximal tubule (as estimated from the shrinking-drop technique) by 35%, and reduced fractional reabsorption (as estimated from the tubular fluid-to-plasma ratio) by 20%. In addition the natriuretic plasma increased urine flow, solute-free water clearance, and potassium excretion in rats with hereditary diabetes insipidus, indicating an increase in the delivery of filtrate out of the proximal tubule to the more distal diluting segments of the nephron. The hormonal inhibition of proximal tubular reabsorption had an extremely rapid onset of action (within seconds after instillation into the tubular lumen) and a short duration of action (less than 30 min after cessation of an intravenous infusion). Inhibitory activity was lost from natriuretic plasma upon dialysis and could be recovered in the dialysate. Dialysates of natriuretic plasma, when injected directly into the tubular lumen, also inhibited proximal reabsorption, indicating an action on the luminal side of the cell.