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

N. Stern, S. Lustig, D. Petrasek, G. Jensen, P. Eggena, D. B. Lee, M. L. Tuck

Research output: Contribution to journalArticlepeer-review

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 II-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 II-mediated aldosterone production.

Original languageEnglish
Pages (from-to)III-31-III-35
JournalHypertension
Volume9
Issue number6 II SUPPL.
StatePublished - 1987
Externally publishedYes

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