The metabolism of exogenous and endogenous antidiuretic hormone in the kidney and liver in vivo.

Negligible antidiuretic activity (less than 0.17 mU./g.) was found in extracts of the kidneys either of unanaesthetized adult rats in normal water balance or of rats in whose blood a rise of the level of endogenous antidiuretic hormone had been induced by ether anaesthesia. Extracts of the livers of unanaesthetized rats had negligible antidiuretic activity (less than 0.06 mU./g.), but liver extracts from rats anaesthetized with ether showed antidiuretic effects equivalent to 0.74+/-0.24 mU. Pitressin/g. liver. When Pitressin was injected intravenously into unanaesthetized rats, small amounts of antidiuretic activity were occasionally found in the livers and the kidneys of animals killed up to 3 min. after the injection but none in animals killed later. Some 3% of the antidiuretic activity of an injected dose of Pitressin was found in the urine and the "dead space" of the kidneys in rats decapitated 3 min. after the intravenous injection. When Pitressin was added to rat kidney homogenate and the mixture was incubated at 38 degrees , only 0.75% of the initial antidiuretic activity was recovered after 30 min. and less than 0.40% after 60 min. Experiments with "glomerular" and "tubular" fractions of rat kidney indicated that the inactivation was essentially due to tubular tissue. It is suggested that, in the rat, the kidneys and perhaps the liver are not only sites of clearance of the antidiuretic hormone but also sites of irreversible inactivation.