Effect of L-NAME, a specific nitric oxide synthase inhibitor, on corticotropin-releasing hormone-elicited ACTH and corticosterone secretion

This study was designed to determine the role of endogenous nitric oxide (N O) in the corticotropin-releasing hormone (CRH)-induced ACTH and corticoste rone secretion, as well as possible involvement of hypothalamic dopamine an d noradrenaline in that secretion in conscious rats. CRH given ip stimulate d dose-dependently the pituitary-adrenocortical activity measured 1 h later . Dexamethasone (0.2 mg/kg ip) injected 1 h before CRH (1 mu g/kg ip) total ly abolished the CRH-elicited ACTH and corticosterone secretion, Indicating a predominantly pituitary site of CRH-evoked stimulation, L-arginine (120 mg/kg ip) and N omega-nitro-L-arginine methyl ester (L-NAME 5-10 mg/kg ip) did not markedly affect the basal plasma ACTH and corticosterone levels. L- NAME given 15 min before CRH markedly, but not significantly, augmented the CRH-induced ACTH response, and enhanced more potently and significantly th e corticosterone response. Pretreatment with L-arginine, a substrate for NO S, slightly diminished the CRH-induced ACTH response and considerably reduc ed the corticosterone response. L-arginine also significantly reversed the L-NAME-evoked increase in the CRH-induced ACTH and corticosterone secretion . L-NAME did not markedly alter the CRH-induced hypothalamic dopamine and n oradrenaline levels, while L-arginine significantly increased noradrenaline level. However, those alterations were not directly correlated with the ob served changes in ACTH and corticosterone secretion. These results indicate that in conscious rats NO plays a marked inhibitory role in the CRH-induce d ACTH secretion and inhibits more potently corticosterone secretion. Hypot halamic dopamine and noradrenaline do not seem to be directly involved in t he observed alterations in ACTH and corticosterone secretion.