Renal and hepatic nitrogen metabolism during NH4Cl ingestion in protein-deprived rats.

Three groups of rats were given either a standard protein diet, a protein-free diet, or a protein-free diet with the inclusion of 0.28 M NH4Cl in their drinking water, for 10 days. Body, liver and kidney masses were decreased similarly in the protein-free and protein-free NH4Cl groups. Ingestion of protein-free diet resulted in profound systemic acidosis in both groups, the simultaneous consumption of NH4Cl having no further effect. The activities of the urea-cycle enzymes carbamoyl-phosphate synthease, ornithine transcarbamoylase, arginosuccinate lyase and arginase were significantly reduced in the protein-free group, and the simultaneous ingestion of NH4Cl had no further effect. These results indicate that ammonium ingestion does not prevent the decrease in urea cycle enzyme activities during a period of dietary-protein deprivation. Renal phosphate-dependent glutaminase activity was unchanged in the protein-free group, but was significantly higher with simultaneous NH4Cl consumption, suggesting that the renal adaptation to acid ingestion is not compromised by a lack of dietary protein. Urinary ammonia excretion also increased in rats consuming protein-free diet and NH4Cl. Urinary urea excretion was greater in rats receiving protein-free diet and NH4Cl than in rats receiving protein-free diet only, at all time-points examined. These data demonstrate that urea synthesis is driven primarily by the need to dispose of protein-derived ammonia rather than bicarbonate.

Alterations in renal and hepatic nitrogen metabolism in rats during HCl ingestion.

The effect of prolonged metabolic acidosis on hepatic and renal enzymes associated with nitrogen metabolism was investigated. The rates of urinary ammonia and urea excretion were also determined. Administration of 9 mmol HCl daily for 8 days resulted in severe metabolic acidosis. The activity of the first two enzymes of the urea cycle, carbamoyl phosphate synthetase (CPS) and ornithine transcarbamoylase (OTC), was 30% greater in chronically acidotic rats than in pair-fed controls. There was also a fivefold increase in renal phosphate-dependent glutaminase (PDG) activity and an 18 to 24-fold increase in renal ammonia excretion. Urea excretion was not constant in the acidotic group, decreasing during the first 4 days and gradually returning to pair-fed control levels between the fourth and eighth day. The return to control levels of urinary urea excretion coincided with the plateau of urinary ammonia excretion that occurred by day 4 in the acidotic group. A similar pattern of urea nitrogen excretion has been observed in both NH4Cl and HCl acidosis, ie, an initial decrease in urea excretion followed by a gradual increase with time. These results suggest that hepatic urea synthesis does not play a significant role in long-term regulation of the acid-base balance in rats during chronic metabolic acidosis.

The effect of ammonium chloride on hepatic and renal metabolism in the rat.

The metabolic effects of an ammonium salt on the liver and kidney were investigated. Rats were allowed free access to a 0.28 M ammonium chloride (NH4Cl) solution for 7- and 8-day periods. Serum urea concentration was significantly increased after 8 days of NH4Cl ingestion. However the following hepatic urea cycle enzymes remained unchanged: CPS, OTC, ASS and ASL. The pattern of urinary urea excretion was variable. When the data for the 7-day period were pooled, there was no significant difference between the control and acidotic groups. However, when they were examined on a daily basis, acidosis significantly decreased urea excretion on day 2. Urea excretion then began to increase, reached the control value on day 4 and was significantly greater than the control value on day 7. Urinary ammonium excretion of the acidotic group was significantly increased on day 2 and continued to rise throughout the 7-day period. Renal phosphate-dependent glutaminase of the acidotic group was significantly increased on the eighth day. These data indicate that NH4Cl ingestion alters the pattern of urea excretion in a manner not previously demonstrated.