Blockade of nitric oxide formation impairs adrenergic-induced ACTH and corticosterone secretion

It has been suggested that adrenergic agents might modulate the L-arginine- NO pathway. Sympathomimetic agonists enhance the basal release of NO, and n oradrenaline increases the synthesis of nitric oxide synthase (NOS) in the medial basal hypothalamus in vitro. In the present study possible involveme nt of NO in central stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by adrenergic agents was investigated in conscious rats. The nitric o xide synthase blocker N-omega-nitro-L-arginine methyl ester (L-NAME 2 and 1 0 mu g) was administered intracerebroventricularly (icv) 15 min before the adrenergic agonist given by the same route; 1 h later the rats were decapit ated. Plasma levels of ACTH and corticosterone were measured. L-NAME signif icantly diminished the ACTH and corticosterone response to phenylephrine (3 0 mu g), an alpha(1)-adrenergic receptor agonist. These hormone responses t o clonidine (10 mu g), an alpha(2)-receptor agonist, were dose-dependently suppressed or totally abolished by L-NAME. A significant rise in the ACTH a nd corticosterone secretion induced by isoprenaline (10 pg), a beta-adrener gic receptor agonist, was only moderately diminished by pretreatment with L -NAME. These results indicate that NOS is considerably involved in central stimulation of the HPA axis by alpha(1)- and alpha(2)-adrenergic receptor a gonists, and that NO mediates the stimulatory action of these agonists on A CTH and corticosterone secretion. The stimulation induced by beta-adrenergi c receptors is only moderately affected by endogenous NO.