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

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Abstract
The rate of disappearance of H3-d-aldosterone from peripheral plasma was studied in dogs. The data were analyzed in terms of a2compartmental model; the volume of distribution, fractional turnover rate, and metabolic clearance rate (MCR) were calculated. The t1/2 of the slow componnt of the disappearance curve was prolonged and the MCR was decreased after hemorrhage, following hypophysectomy, and in experimental low output heart failure, but aldosterone metabolism was not detectably altered during Na depletion or in high output heart failure. Consequently, a decreased rate of aldosterone metabolism contributed to the hyperaldo-steronemia of hemorrhage and experimental low output heart failure and provided a mechanism for counteracting the low secretion rate of aldosterone in experimental hypopituitarism. Exhaustive exercise in dogs with low output heart failure failed to produce a further decrease in the low rate of aldosterone metabolism. An Inverse relationship was observed between the t,1/2 of the slow component of the disappearance curves and the MCR. Measurements of the hepatic extraction of aldosterone demonstrated almost complete removal of the hormone in one circulation of blood through the liver in normal dogs, following acute blood loss, during Na depletion, after hypophysectomy, and during severe congestion of the liver secondary to thoracic caval constriction. This finding suggests that the hepatic mechanism for metabolism of aldosterone is flow-limited, since previous study has indicated negligible extrahepatic clearance of aldosterone from plasma. Also, there is evidence that hepatic blood flow is decreased in the present conditions with a low rate of aldosterone metabolism.