Role of nitric oxide in the vasopressin-induced corticosterone secretion in rats

The presence of nitric oxide synthase (NOS) in hypothalamic structures which control the activity of the hypothalamic-pituitary-adrenal (HPA) axis suggests a role for NO in regulation of ACTH and corticosterone secretion. We investigated the involvement of NO in the corticosterone secretion induced by vasopressin (AVP), a potent coregulator of the HPA activity. AVP injected i.p. was, on a molar basis, considerably more potent than administered intracerebroventricularly in inducing corticosterone secretion. This finding suggests a preferential action of AVP on pituitary corticotrop receptors, but not on central structures involved in stimulation of the HPA axis. Dexamethasone given before AVP totally abolished the AVP-elicited corticosterone response by a feedback mechanism and/or inhibition of the phospholipase A2 activity and prostaglandin synthesis. Pretreatment with the NOS inhibitors L-NAME and L-NNA augmented significantly and to a similar extent the corticosterone response to AVP administered both systemically and centrally and L-NNA was found to be more potent in this respect. Pretreatment with L-arginine markedly reduced the AVP-induced corticosterone response. These results suggest that endogenous nitric oxide is significantly involved in the AVP-elicited corticosterone secretion and NO-induced alterations in the prostaglandin synthesis may participate in this action.