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 micrograms/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 micrograms/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, as well as 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.
D000311:Adrenal Glands / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D009539:Nicotinic Acids / Q000494:pharmacology*; D009553:Nimodipine; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014020:Tissue Extracts / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009539:Nicotinic Acids; D014020:Tissue Extracts; D009553:Nimodipine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone