The Effect of Spironolactone on the Hepatic Metabolism of Aldosterone in Male Rats*

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Abstract
The rate of excretion of aldosterone radiometabolites into the bile was markedly increased in male rats after treatment with a single, acute, pharmacological dose of spironolactone 15 min before the i.v. injection of [3H]aldosterone. In 1 h, 42% of the injected 3H radioactivity was excreted in the bile of spironolactone-treated male rats compared with 27% in the control rats. This treatment of the males with spironolactone led to an increased rate of excretion of aldosterone metabolites in the bile similar to that previously observed in both gonadectomized male and intact female rats. Sephadex DEAP-LH-20 column chromatography demonstrated significant differences in the types of conjugates of aldosterone and its metabolites present in the bile of male rats treated with spironolactone compared to the controls. The bile of male rats treated with spironolactone contained significantly greater quantities of mono- and disulfates of aldosterone and its metabolites and significantly smaller quantities of neutral metabolities and glucuronides of aldosterone and its metabolites. The types of conjugates of aldosterone observed in the bile of the spironolactone-treated male rats were similar to those typically observed in the bile of female rats and seem to account for the increased biliary excretion of aldosterone radiometabolites in these rats. The rapid effect of spironolactone on the hepatic metabolism and conjugation of aldosterone suggests that spironolactone may act at a locus in the liver, preventing the androgenic control of the hepatic metabolism of aldosterone in male rats.