Organ Distribution of N Following Intravenous Injection of [N]Ammonia into Portacaval-Shunted Rats.

Ammonia is neurotoxic, and chronic hyperammonemia is thought to be a major contributing factor to hepatic encephalopathy in patients with liver disease. Portacaval shunting of rats is used as an animal model to study the detrimental metabolic effects of elevated ammonia levels on body tissues, particularly brain and testes that are deleteriously targeted by high blood ammonia. In normal adult rats, the initial uptake of label (expressed as relative concentration) in these organs was relatively low following a bolus intravenous injection of [N]ammonia compared with lungs, kidneys, liver, and some other organs. The objective of the present study was to determine the distribution of label following intravenous administration of [N]ammonia among 14 organs in portacaval-shunted rats at 12 weeks after shunt construction. At an early time point (12 s) following administration of [N]ammonia the relative concentration of label was highest in lung with lower, but still appreciable relative concentrations in kidney and heart. Clearance of N from blood and kidney tended to be slower in portacaval-shunted rats versus normal rats during the 2-10 min interval after the injection. At later times post injection, brain and testes tended to have higher-than-normal N levels, whereas many other tissues had similar levels in both groups. Thus, reduced removal of ammonia from circulating blood by the liver diverts more ammonia to extrahepatic tissues, including brain and testes, and alters the nitrogen homeostasis in these tissues. These results emphasize the importance of treatment paradigms designed to reduce blood ammonia levels in patients with liver disease.