Modifications of bile secretion and liver microsomal enzymes by aldosterone and spironolactone

During a period of two weeks male adult albino rabbits received a daily subcutaneous injection of: Group I: 0.1 ml of 0.9% sodium chloride solution/kg b. wt (control); Group II: 150 micrograms spironolactone/kg b. wt. Twenty-four hours after the final injection, the animals were anesthesized, the bile duct was cannulated (after ligation of the cystic duct) and bile was collected for two hours. At the end of the experiment, the liver was removed, weighed and submitted for cytochrome P-450 measurement and microscopic analyses. Red blood cell sodium content was measured in the aldosterone group before and after treatment. Compared with control animals, we found the following: (I) The bile flow, the biliary sodium and bile acid excretion were significantly decreased (P less than 0.01) in aldosterone-treated animals and significantly increased (P less than 0.01) in spironolactone treated ones. (II) In animals treated with aldosterone and in those treated with spironolactone, liver cytochrome P-450 was significantly increased (P less than 0.001). (III) In livers of both aldosterone and spironolactone-treated animals, there were hyaline changes in the hepatocytes without necrosis or steatosis. Electron microscope studies revealed a proliferation of smooth endoplasmic reticulum in livers of both groups. (IV) Red blood cell sodium content was significantly increased (P less than 0.001) after treatment with aldosterone. In conclusion, aldosterone and spironolactone have the opposite effect on bile secretion. Both are liver microsomal enzyme inducers. A correlation between bile secretion and liver enzyme induction seems improbable.