CRH-mediated pituitary-adrenal responses are inhibited by nifedipine in humans

Sustained CRH-stimulated ACTH release in vitro depends on Ca2+ influx and is inhibited 30-40%, but not delayed, by dihydropyridine Ca2+ channel blockers. In five normal humans, we found that nifedipine pretreatment reduced integrated ACTH responses to the CRH-mediated stimulus of fenfluramine by 28% and cortisol responses by 34%, results comparable with those from in vitro reports. Nifedipine did not alter the timing of peak hormonal responses. We conclude that (1) in humans, nifedipine inhibits ACTH release by fenfluramine by blocking Ca2+ influx via L-type channels in corticotrophs; (2) the magnitude of fenfluramine-stimulated CRH release is probably unaltered by nifedipine and (3) because the timing is unaltered, nifedipine does not affect the rate of CRH delivery to the corticotroph.