Cyclosporin a-induced hyperreninemic hypoaldosteronism: A model of adrenal resistance to angiotensin II

Abstract

We studied the effects of cyclosporin A on the renin-aldosterone axis in Sprague-Dawley rats. Two weeks of intragastric administration of cyclosporin A (5 mg/kg/day or 20 mg/kg/day) resulted in large increases in plasma renin concentration (23 ± 5, 70 ±12, and 79 ± 11 ng/ml/hr in control rats and rats receiving 5 mg and 20 mg of cyclosporin A, respectively), with no parallel increments in plasma aldosterone. In vitro angiotensin II (ANG II)-stimulated aldosterone secretion by zona glomerulosa cells obtained from cyclosporin A-treated rats was also reduced (4.8 ± 0.5, 1.5 ± 0.2, and 0.2 ± 0.2 ng/105 cells in control rats and rats receiving 5 mg and 20 mg of cyclosporin A, respectively). In contrast, in vitro aldosterone response to graded increments of potassium (3.7-10.7 mmol/L) or adrenocorticotropic hormone (ACTH) (10-11-10-8 M) was preserved in cyclosporin A-treated rats. When added in vitro to zona glomerulosa cells from untreated rats, cyclosporin A also attenuated ANG Il-stimulated aldosterone secretion, but did not affect potassium or ACTH-mediated aldosterone production. Thus, cyclosporin A-induced hyperreninemic hypoaldosteronism in the rat depends on opposing renal and adrenal effects, with a direct or feedback stimulation of renin secretion and a specific blockade of ANG H-mediated aldosterone production. © 1987 American Heart Association, Inc.