The role of anaerobic metabolism in the urine concentration mechanism

Rats maintained in a state of chronic water diuresis were given as osmotic loads intraperitoneally, 10 percent of their body weight of either 0.45 percent saline or 10 percent mannitol in water. Faeces-free urines were collected under the following experimental protocols: osmotic diuresis, osmotic diuresis plus ADH and osmotic diuresis plus ADH plus metabolic inhibitors. A number of inhibitors of aerobic and anaerobic metabolism were used. Samples of kidney cortex medulla and papilla were also collected and analysed. The results obtained show that rats maintained in chronic water diuresis excreted a dilute urine and had largely dissipated their cortico-medullary gradients of sodium and urea. Under ADH stimulation, the rats excreted a concentrated urine with marked restoration of the cortico-medullary gradients. These effects were markedly inhibited by iodo-acetate and fluoride, but not by 2-4 dinitrophenol, hydroxylamine HCl or cyanide. The results suggest that a large proportion of the energy required for the creation of a hypertonic medulla, and hence the formation of a concentrated urine, is derived from anaerobic glycolysis (AU)