THE EFFECTS OF CHRONIC HEPATIC VENOUS CONGESTION ON THE METABOLISM OF d,l-ALDOSTERONE AND d-ALDOSTERONE*

Abstract

The biological half-lives of tritiated d, 1- and d-aldosterone in normal dogs were 34 and 27 minutes, respectively. After thoracic caval constriction and in the presence of marked chronic hepatic venous congestion the t1/2 for both d, 1-aldosterone and d-aldosterone was markedly prolonged. Subsequent hepa-tectomy resulted in an almost flat disappearance curve of d, 1-aldosterone. Analysis of the data in terms of a two-compartmental model showed a decreased rate of turnover of both d, 1- and d-aldosterone by both the inner and outer compartments in dogs with caval constriction. The data provide evidence that a decreased rate of metabolism of aldosterone may contribute to the hyperaldosteronemia in clinical states with severe chronic hepatic congestion, as in rightsided congestive heart failure. However, in dogs with caval constriction the more consistent occurrence and marked degree of hypersecretion of aldosterone indicate that increased secretion is the primary mechanism leading to hyperaldosteronemia. Urine was found to be the major excretory route for d,l-aldos-terone and its metabolites. Only trace amounts of radioactivity from H3-d, 1-aldosterone were recovered in bile. Saline washes of red blood cells demonstrated the presence of H3-d-aldosterone in, adsorbed on, or bound to the red blood cells. Studies by equilibrium dialysis of the degree of binding of d, 1- and d-aldosterone to plasma proteins showed 27 to 43 per cent binding in the dog in contrast to approximately 70 per cent binding to normal human plasma protein. No difference in the degree of binding of aldosterone was observed between plasma from normal animals and dogs with caval constriction.