INCREASED HEPATIC CAPACITY OF UREA SYNTHESIS IN ACUTE AND CHRONIC UREMIA IN RATS

We studied whole body nitrogen balance in female rats for 28 days after induction of experimental uraemia by 5/6 nephrectomy and at the same time the kinetics of hepatic urea synthesis by means of the in vivo capacity of urea synthesis. The N-balance of 5 uraemic rats kept in metabolic cages was negative on day 2, and positive but only half of control on day 28. In between, it was normal. The uraemic rats lost weight during the first week, and later only slowly regained their initial weight. The capacity for urea synthesis was determined during alanine loading in 5 unoperated controls, in uraemic rats in groups of 5 on days 2, 7, 14, 21, and 28, and correspondingly in sham operated rats. In the control rats the capacity was 8.9 +/- 0.7-mu-mol/(min 100 g BW) and the same in sham operated rats. In uraemic rats the capacity increased to 17.1 +/- 2.0-mu-mol/(min 100 g BW) (p < 0.01) 2 days after partial nephrectomy. On day 7, the capacity fell to 5.5 +/- 1.0 (not different from initial values), and thereafter again gradually increased to 16.5 +/- 1.5-mu-mol/(min 100 g BW) on day 28. The early increase in the capacity may be related to glucagon, that nearly doubled on day 2, but not on day 28. The hepatic capacity for urea synthesis doubles biphasically: acutely and after 4 weeks of experimental uraemia. This may play a role in the reduction in N-balance, since an increase in the capacity implies larger hepatic amino-N conversion at any blood amino-acid concentration.