Using dose-response curves, the dose of NH4Ac inducing
coma in one-half of the animals was increased by 60 to 80% after 1 mmol of
arginine. The larger increase occurred in larger rats but was not proportional to the increase in weight. Incremental subcoma doses of NH4 raised the amount of NH4 required for inducing
coma and the brain level of
ammonia at the point of
coma. After a
portacaval shunt the results were similar, although lower doses of NH4 were required from the beginning. Blood ammonias after a loading dose (1.25 mmol) of NH4 were influenced by the duration of a preinfusion of NH4 and by the preinjection of various
amino acids involved in the disposal of NH4 in the
urea cycle. The amount of reduction in blood
ammonia by
ornithine and
arginine compounds was less the longer the preinfusion of NH4. Blood
ammonia was not lowered by
glutamate at any time but was increased with longer preinfusion periods.
Hepatectomy (Hx) reduced the removal of an NH4 load. After a modest load (0.85 mmol) of NH4, blood
ammonia increased 5-fold, over that of
sham-operated rats, with 70% Hx and 15-fold with 90% Hx.
Ornithine reduced these blood ammonias by about 50%.
Arginine had no effect. These studies indicate ways of reducing toxicity of NH4 and factors that predispose to or enhance toxicity.