Urea synthesis was examined in experimental
uremia using the isolated perfused rat liver in order to assure strict control of substrate (NH4Cl) presented to the liver. Acute
uremia was created in female Sprague-Dawley rats by bilateral
nephrectomy (n = 7) 48 h prior to studies. Chronic
uremia (8--14 weeks) was produced by right
nephrectomy and segmental
infarction of the left kidney in 7 rats. At infusion rates of NH4Cl (8.3 mumol/min) which resulted in prehepatic perfusate
ammonia levels approximately twice the previously described Km value, livers of chronically uremic rats had slightly higher rates of
urea production than controls (controls: 0.41 +/- 0.03; chronic
uremia: 0.54 +/- 0.04 mumol/min/g of wet liver weight; p less than 0.02). In acute
uremia,
urea production was higher (0.66 +/- 0.05 mumol/min/g) than in
sham-operated rats (0.59 +/- 0.05 mumol/min/g) but the differences did not achieve statistical significance. Simultaneously performed
taurocholate transport studies did not reveal significant functional differences between the livers of uremic and control animals. The data suggest that
urea production by livers of uremic rats is increased when compared to that of control animals.