Conjugation of 1,2-3H-Aldosterone in Human Liver and Kidneys and Renal Extraction of Aldosterone and Labeled Conjugates from Blood Plasma

Abstract

Tritium-labeled aldosterone and the principal labeled conjugates derived from aldosterone were measured in arterial plasma during a constant infusion of 1,2-³H-aldosterone. Acid-labile conjugate was present in a concentration less than ⅕ that of aldosterone. After plasma was treated with betaglucuronidase, labeled tetrahydroaldosterone and a less polar fraction could be extracted. The concentration of tritium found as total conjugates was equal to or greater than the concentration of ³H-aldosterone in plasma. Blood was obtained from a hepatic or renal vein through a venous catheter. The conjugates were present in hepatic vein plasma in concentrations approximately 40% higher than in simultaneously drawn samples of arterial plasma, indicating production of these conjugates in the liver. Approximately 20% of free aldosterone in arterial plasma was removed from blood passing through the kidney, corresponding to the fraction filtered through the glomeruli: but only 1.3–3.6% of the estimated amount of filtered aldosterone appeared in the urine. The acid-labile conjugate, on the other hand, appeared in urine at a greater rate than could be expected from the renal extraction ratio of this metabolite (25–46%). Conversion of free aldosterone to acidlabile conjugate in the kidney would account for these findings. The plasma clearance and hepatic extraction of free aldosterone were reduced in patients with advanced congestive heart failure, as previously reported. The increased concentrations of labeled conjugates in plasma of patients with heart failure indicated that renal clearances of conjugates were below normal.