THE PRODUCTION OF HYPERTENSION, NEPHROSCLEROSIS AND CARDIAC LESIONS BY METHYLANDROSTENEDIOL TREATMENT IN THE RAT1

Abstract

Effects of chronic admn. of methylandrostenediol (MAD) and desoxycortico. sterone acetate (DCA) were studied in the unilaterally nephrecto-mized, female rat allowed 1% NaCl to drink. When these steroids were given alone in doses of 2.5 mg./day and 0.5 mg./day, respectively, slight hypertension developed only in the MAD treated animals. When both steroids were given, hypertension was more pronounced and definite anatomical changes were detected in the kidneys and heart. Admn. of MAD and DCA in daily doses of 10 mg. and 2 mg., respectively,for 6 wks. produced a pro- gressive increase in the saline intake and a rise in the blood pressure of the treated animals. At autopsy the DCA treated rats showed renal and cardiac hypertrophy, marked arteriolar nephrosclerosis, glomerular hyalinization, tubular dilatation and cast formation, and cardiac lesions characterized by vascular and interstitial hyaline and granulomatous formation. Animals treated with MAD showed significantly greater renal hypertrophy, almost identical cardiac enlargement, and similar but more marked renal and cardiac lesions. In addition, MAD produced a peculiar adrenal cortical necrosis, characterized by hyaline material in the sinusoids and intracellular hyaline or colloid inclusion bodies. Marked thymic involution was characteristic of the rats treated with MAD. While the present expts. illus. certain similarities in the changes produced by the chronic admn. of these steroids to unilaterally nephrectomized, salt-treated rats, it is felt that there are sufficient variations to warrant the conclusion that fundamental differences exist in their mechanism of action.