Renal Regulation of Urea Excretion in Sheep

Abstract

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.