Effect of nimodipine, a new calcium antagonist, on ACTH and corticosterone release 'in vivo' and 'in vitro'

Intravenous injection of nimodipine (1, 10 and 100 μg/Kg) determined a sharp and short-lasting increase in plasma ACTH levels. No change was observed in corticosterone plasma concentration. Intracerebroventricular injection of nimodipine (up to 50 μg/rat) did not alter hormone plasma levels. In in vitro experiments, nimodipine (10-8, 10-7 and 10-6 M) did not modify basal and hypothalamic extract-stimulated ACTH release from pituitary tissue, nor basal release of corticosterone from isolated adrenal glands. However, when adrenal tissue production of corticosterone was stimulated with ACTH, nimodipine (10-8, 10-7 and 10-6 M) showed a powerful and long-lasting inhibitory effect. Data indicate that nimodipine could influence pituitary-adrenal axis by primarily reducing the responsiveness of adrenal glands to ACTH, and exclude a direct effect on hypophysis. It is suggested that the nimodipine-induced reduction of adrenal tissue responsiveness could trigger in vivo a reflex increase in ACTH release, which, in turn, might avoid a decrease in plasma corticosterone levels.