Antidiuretic hormone inactivation by isolated perfused rat liver

Abstract

The characteristics of inactivation of U.S.P. posterior pituitary standard (ADH) by the isolated rat liver have been studied by 2 experimental methods: the disappearance of ADH from the circulating perfusate of continuously perfused livers, and the fractional inactivation of ADH added to blood as a result of a single passage of the blood through the isolated liver. The hepatic clearance rate of ADH was concentration dependent; average fractions inactivated or extraction ratios in single-passage experiments ranged from 0.24 at 15-25 [mu]U ADH/ml plasma to 0.63 at 1,000-5,000 [mu]V/ml. Although ADH clearance by the rat liver may be high and relatively constant at blood ADH concentrations above 100 [mu]U/ml, consistent with previously reported in vivo experiments, the present studies indicate that the clearance rate is reduced by at least 50% in the physiological range of blood concentrations. Inactivation did not appear to depend on oxidative metabolism, and no ADH activity was found in the bile of perfused livers. Preliminary experiments indicate that during continuous perf usion of the isolated liver an ADH-inactivating factor is released into the blood perfusate.