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

Abstract

In 1950 Deming and Luetscher demonstrated increased salt-retaining activity in urine from patients with congestive heart failure (1). In 1953 aldosterone was isolated (2), and subsequently the urinary excretion of this hormone was found to be elevated in nearly all the clinical states associated with edema. Two possible mechanisms could lead to an increase in the plasma level of aldosterone and thus to an increase in urinary aldosterone excretion: 1) hypersecretion of aldosterone, and 2) a decreased rate of metabolism of the hormone. In 1957, it was demonstrated that a sixfold increase in aldosterone secretion occurred in dogs with experimental right heart failure and in dogs with thoracic inferior vena caval constriction (3). The possibility of decreased metabolism of aldosterone was suggested by Yates, Urquhart and Herbst (4) who found a decrease in the 4,5-steroid reductase activity for inactivation of aldosterone by liver tissue from rats subjected to chronic passive venous congestion. They suggested that a decreased rate of reduction of ring A of aldosterone might increase the plasmal level of the hormone in these animals. The primary purpose of the present study was to evaluate the possibility of a decreased rate of metabolism of aldosterone by the congested liver. The disappearance of H3-aldosterone from plasma was studied in dogs with chronic hepatic venous congestion secondary to thoracic inferior vena caval constriction and in normal animals. In addition, several aspects of the metabolism of dl-aldosterone were studied including the urinary and biliary excretion of * Reported in preliminary form to the Endocrine Society, June, 1960, and at the Laurentian Hormone Conference, Sept., 1960. total tritium radioactivity, the disappearance of total methylene chloride-extractable radioactivity from the plasma, the effect of hepatectomy on the biological half-life (ti) of aldosterone, and binding of H3-aldosterone to plasma protein. At the time these studies were performed tritiated d-aldosterone was not available; recently, d-aldosterone has been tritiated and additional observations have been made with the natural hormone. METHODSStudies with d,l-aldosterone. The disappearance of H3-d,l-aldosterone from peripheral plasma was determined in 9 normal dogs before and after constriction of the thoracic inferior vena cava, and in one additional dog after caval constriction. Ten or 20 ,sc (7 to 21 pug) of the d,l-form of randomly ring-labeled H3-aldosterone, with a specific activity ranging from 1.0 to 3.0 MAc per 1ug was injected intravenously; the efficiency of the liquid scintillation spectrometer was approximately 25 per cent. The concentration of true H3-aldosterone in peripheral plasma was measured at intervals of 5, 10,15,20, 30, 45, 60, and 90 minutes. In the dogs with thoracic inferior vena caval constriction, large volumes of ascitic fluid formed and sodium retention was almost complete. In a preliminary experiment it was found that equilibration of H3-aldosterone between ascitic fluid and plasma was v...

Metabolism of Aldosterone in Several Experimental Situations with Altered Aldosterone Secretion*

“…In an earlier study (1), the rate of metabolism of aldosterone was found to be decreased in dogs with chronic passive congestion of the liver secondary to thoracic inferior vena caval constriction. After hepatectomy of these animals and of normal dogs, the metabolism of aldosterone was almost abolished.…”

“…The concentration of HW-d-aldosterone was measured in peripheral venous plasma by a slight modification (1) of the double isotope derivative assay (8), and two additional changes were made for the present study. First, the samples were run through a third chromatography; a cyclohexane (100 parts), benzene (50 parts), methanol (100 parts), and water (25 parts) system was used, and the chromatogram was developed for 10 hours.…”

Effect of neomycin on exchangeable pools of cholesterol in the steady state

“…[ 13] In addition to M., the three other quantities yielded uniquely by the compartment analysis are obtained from equations 1, 2, 10 as (14-17) [14] [ Eb/MOA = n(1 -u) [10] [26] [27] [28]…”

The metabolic clearance rate of progesterone in males and ovariectomized females.

“…Soiva, Haskins, and McCafferty showed the rapid disappearance of plasma radioactivity after the injection of 276 jug progesterone-4-14C (11). Nine minutes after the single injection of progesterone-4-14C Zander showed the presence in the plasma of pregnanolone (5,8 pregnane 3a-ol, 20-one), pregnanediol (5,8 pregnane 3a-20a-diol), and 20a-hydroxy-4 pregnen, 3-one). Short and Eton (12) calculated tj to be 5 minutes in pregnant women after the removal of the placenta at Cesarean section.…”