METABOLISM OF SALT-RETAINING HORMONE BY SURVIVING LIVER SLICES 1

Abstract

Active salt retaining hormone, considered to be aldosterone and obtained from urine extracts collected from patients with cirrhosis of the liver, preeclamptic toxemia and congestive heart failure, was incubated in Warburg flasks with rat and human liver slices for periods of one hour, after which the flask contents were re-extracted and the salt-retaining potency re-assayed. The tissue was respiring actively throughout the experiment and QO2 values were within the usual range. Control experiments were planned with cyanide inhibition of respiration and with boiled liver slices. Additional experiments were done under anaerobic conditions and also using kidney slices. Comparison of pre and post incubation measurements of aldosterone activity, indicated almost complete inactivation of the steroid under aerobic conditions, with some statistically significant impairment of this function anaerobically. Cyanide completely inhibited respiration but produced complete inactivation of the hormone, through another (non-biological, chemical) mechanism. It is possible that failure of adequate inactivation of this steroid compound by the liver, may account, in part for the accumulation of excessively high urinary titers of aldosterone, so regularly found in diseases with marked Na and fluid retention. Such inactivation under physiological conditions may represent an additional homeostatic mechanism to prevent accumulation of excessive amounts of "active" hormone.