In a number of mammalian kidneys a close correlation was found between renal medullary thickness and ability to concentrate electrolytes in the urine, indicating that both outer and inner zone of the medulla act as a countercurrent multiplier system. Further evidence for this assumption was furnished through studies of the distribution of urea and electrolytes in different kidney types during antidiuresis. The beaver with 100% short-looped nephrons, the rabbit with 44% long-looped nephrons, and the desert rodent Psammomys with 100% long-looped nephrons were studied. In all three kidney types sodium and urea concentrations increased to approximately the same level in the outer zone of the medulla. In the rabbit and Psammomys kidneys a considerable increase in sodium concentration was found through the inner zone of the medulla. This can best be explained if we assume that the sodium pump, which has been demonstrated in the thick ascending limb of the loop of Henle, functions in a similar manner in the thin limb.

Fluid was collected by micropuncture from proximal and distal convolutions of anesthetized rats and analyzed for inulin, sodium, urea, and total osmotically active solute. The proximal fluid/plasma (F/P) sodium ratio was not significantly different from unity in antidiuretic animals, but was as low as 0.78 during mannitol diuresis. The distal F/P sodium ratio averaged 0.62 in antidiuresis, and 0.24 during osmotic diuresis. The data are interpreted to indicate active sodium transport by both proximal and distal convolutions. The F/P ratios for inulin, urea, and total osmotically active solute are in general agreement with previous studies.

In order to elucidate the renal mechanism for the regulation of urea excretion the urea clearance and the GFR were studied in sheep during normal and low protein intake in a range of urine flows from extreme osmotic diuresis to minimal flows. Differences in the effects of osmotic and water diureses and the effects of abrupt changes in rate of urine flow were also studied. In sheep on normal protein intake the urea/inulin clearance ratio was constant in the range of urine flows corresponding to inulin U/P ratios from 10 to 500. On low protein intake the urea/inulin clearance ratio decreased markedly with decreasing urine flow. At extremely high urine flows no difference was found between the urea/inulin clearance ratios on different diets. Regulation was found to be independent of GFR, plasma urea concentration and osmotic load and must therefore be on the tubular level. Observations during abrupt changes in urine flow showed that the urea clearance is not only abnormally high during increasing flows but also abnormally low during a sudden decrease in flow. The first phenomenon is known as ‘exaltation,’ and we have termed the latter phenomenon ‘abatement.’ The data on exaltation and abatement and on the effects of urine flow are consistent with a previously suggested hypothesis that the excretion of urea in the mammalian kidney is brought about through a regulated active transport of urea, accentuated by a countercurrent multiplier system represented by Henle's loops and vasa recta.