title: 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 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/10(5) 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.
authors.forename: N
authors.initials: N
authors.lastname: Stern
authors.forename: S
authors.initials: S
authors.lastname: Lustig
authors.forename: D
authors.initials: D
authors.lastname: Petrasek
authors.forename: G
authors.initials: G
authors.lastname: Jensen
authors.forename: P
authors.initials: P
authors.lastname: Eggena
authors.forename: D B
authors.initials: DB
authors.lastname: Lee
authors.forename: M L
authors.initials: ML
authors.lastname: Tuck
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects*; D000450:Aldosterone / Q000096:biosynthesis / Q000097:blood*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D004351:Drug Resistance; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood*
chemical_list: D003524:Cyclosporins; D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin