The early renal metabolic response was studied in rats made acidotic by oral feeding of
ammonium chloride. 2 hr after feeding of
ammonium chloride there was already significant
acidosis. Urinary
ammonia also increased after
ammonium chloride ingestion and at 1(1/2) hr was significantly elevated. In vitro gluconeogenesis by renal cortical slices was increased at 2 hr and thereafter increased steadily.
Ammonia production by the same slices was also increased at 2 hr, but thereafter fell and at 6 hr had decreased to levels which, although higher than those of the control, were lower than those obtained from the rats acidotic for only 2 hr. There was no correlation between in vitro gluconeogenesis and
ammonia production by kidney slices from rats during the first 6 hr of
acidosis, but after 48 hr of
ammonium chloride feeding, these two processes were significantly correlated. The early increase in renal gluconeogenesis was demonstrable with both
glutamine and
succinate as substrates. The activity of the
enzyme phosphoenolpyruvate carboxykinase was increased after 4-6 hr of
acidosis. During this time there was a decrease in renal
RNA synthesis as shown by decreased uptake of orotic acid-(5)H into
RNA. Metabolic intermediates were also measured in quick-frozen kidneys at varying times after induction of
acidosis. There was an immediate rise in
aspartate and a fall in
alpha-ketoglutarate and
malate levels. There was never any difference in
pyruvate or
lactate levels or
lactate:
pyruvate ratios between control and acidotic rats.
Phosphoenolpyruvate rose significantly after 6 hr of
acidosis. All the data indicate that increased gluconeogenesis is an early response to
metabolic acidosis and will facilitate
ammonia production by utilization of
glutamate which inhibits the
glutaminase I
enzyme. The pattern of change in metabolic intermediates can also be interpreted as showing that there is not only enhanced gluconeogenesis, but also that there may be significant increase of activity of
glutaminase II as part of the very early response to
metabolic acidosis.