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

Abstract

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. It was suggested that the decreased aldosterone metabolism during liver congestion might be secondary to decreased hepatic blood flow and associated hepatic anoxia. More recently, Tait and his colleagues (2, 3) have provided evidence that the rate of hepatic blood flow is one of the primary determinants of the rate of aldosterone metabolism.The present observations were undertaken to examine the metabolism of aldosterone in several experimental situations in which altered aldosterone secretion occurs and in which there are known or suspected alterations in liver blood flow. The primary objectives were twofold: 1) to define the distribution, metabolic clearance rate (MCR), and hepatic extraction of aldosterone, and 2) to determine the contribution of altered aldosterone metabolism to the peripheral plasma level of aldosterone. Aldosterone metabolism was studied following acute hemorrhage, in dogs depleted of sodium, and in dogs with chronic experimental heart failure. Observations were made in both low and high output failure because hepatic blood flow is reduced in the former and, presumably, normal or elevated in the latter situation. Since exercise greatly reduces the blood flow through the liver in patients with heart failure (4), observations were made before and during ex- hausting exercise in dogs with low output heart failure. The metabolism of aldosterone was also studied in hypophysectomized dogs; in this situation there is a low rather than a high rate of aldosterone secretion, and hepatic blood flow is probably reduced. Finally, the hepatic extraction of aldosterone was measured in several experimental situations. MethodsThe rate of metabolism of aldosterone was studied by observing the rate of disappearance of 1,2-H'-d-aldosterone from peripheral plasma; single iv injections of 12 X 10' cpm of 1,2-H3-d-aldosterone with a SA of 100 Acc per ug were made. The efficiency of the liquid scintillation spectrometer was approximately 25%b. Peripheral venous blood samples of 20 ml were drawn at 5, 10, 15,20, 30, 45, 60, 75, and 90 minutes, and plasma was analyzed for true H3-d-aldosterone. The dogs weighed from 17 to 22 kg.To study the effects of hemorrhage, 30 ml of arterial blood per kg body weight was removed over a 5-to 15-minute period in nine dogs anesthetized with Na pentobarbital. As soon as the arterial pressure had stabilized, tritiated aldosterone was injected, and peripheral venous blood samples were obtained. Arterial pressure was measured continuously throughout the experiment by means of a Statham strain gauge and a Sanborn recording system. As a control experiment, the disappearance of tritiated aldosterone was studied in a series of seven normal dogs anesthetized similarly.Sodium depletion was ...

Plasma Volume in Cirrhosis of the Liver: Its Relation of Portal Hypertension, Ascites, and Renal Failure*

“…The following three possibilities occur to us: 1) The portacaval anastomosis, by decreasing hepatic blood flow, might keep the plasma volume from falling to normal. Evidence has been presented recently to show that hepatic degradation of aldosterone is dependent on liver blood flow (52)(53)(54), and it is possible that a reduction in hepatic blood flow produced by portacaval anastomosis of either the end-to-side or side-to-side variety (36) could elevate the plasma aldosterone concentration sufficiently to keep the plasma volume expanded.…”

Plasma Renin in Chronic Experimental Heart Failure and during Renal Sodium "Escape" from Mineralocorticoids

“…A parallel functional change which is secondary to decreased hepatic blood flow is the decreased plasma clearance of aldosterone (13).…”

Distribution, conjugation, and excretion of labeled aldosterone in congestive heart failure and in controls with normal circulation: development and testing of a model with an analog computer.

“…Tait, Tait, Little, and Laumas (1) described the disappearance of aldosterone from plasma of normal man in terms of a two compartment system. Davis, Olichney, Brown, and Binnion (2) showed that the volumes of distribution and rates of clearance of aldosterone are reduced in dogs with experimental heart failure and low cardiac output. Our findings indicate that marked alterations in distribution and clearance of aldosterone are present in patients with congestive failure.…”