Influence of nitric oxide synthase inhibitors on the vasopressin-induced pituitary-adrenocortical activity and hypothalamic catecholamine levels

In the present study the role of endogenous nitric oxide (NO) in the vasopr essin-induced ACTH and corticosterone secretion was investigated in conscio us rats, Vasopressin (AVP 5 mu g/kg ip) considerably augmented ACTH and cor ticosterone secretion, L-arginine (120 and 300 mg/kg ip) did not significan tly alter the AVP-induced secretion of those hormones. Nitric oxide synthas e (NOS) blockers N-omega-nitro-L-arginine (L-NNA) and its methyl ester (L-N AME) given ip 15 min before AVP markedly increased the AVP-induced ACTH sec retion, L-NNA (2 mg/kg) more potently and significantly increased the AVP-i nduced ACTH secretion, whereas L-NAME elicited a weaker and not significant effect. Both those NOS antagonists intensified significantly and to a simi lar extent the AVP-induced corticosterone secretion, L-arginine (120 mg/kg ip) reversed the L-NNA-induced rise in the AVP-stimulated ACTH secretion an d substantially diminished the accompanying corticosterone secretion. Neith er vasopressin alone nor in combination with L-arginine and L-NAME evoked a ny significant alterations in the hypothalamic noradrenaline and dopamine l evels. L-NNA (2 and 10 mg/kg ip) elicited a dose dependent and significant decrease in the hypothalamic noradrenaline level. The hypothalamic dopamine level was not significantly altered by any treatment. These results indica te that in conscious rats endogenous NO has an inhibitory influence on the AVP-induced increase in ACTH and corticosterone secretion. L-NNA is signifi cantly more potent than L-NAME in increasing the AVP-induced ACTH secretion , This may be connected with a considerable increase by L-NNA of hypothalam ic noradrenergic system activation which stimulates the pituitary-adrenal a xis in addition to specific inhibition of NOS.