Involvement of nitric oxide in central histaminergic stimulation of the hypothalamic-pituitary-adrenal axis

Brain histamine participates in central regulation of the hypothalamic-pitu itary-adrenal (HPA) axis. Endogenous nitric oxide (NO) modulates signal tra nsduction of some neurotransmitters involved in activation of the HPA axis. In the present study we investigated whether endogenous NO and histaminerg ic systems in the rat brain interact in their regulation of ACTH and cortic osterone secretion. Histamine (50 mug), histamine-trifluoromethyl-toluidide derivative (HTMT, 75 mug) a selective and potent H-1-receptor agonist, and amthamine (75 mug) a H-2-receptor agonist given intracerebroventricularly (i.c.v.) considerably increased ACTH and corticosterone secretion 1 h after administration. A potent and competitive inhibitor of rat brain neuronal N O synthase, (NOS), 7-nitroindazole (7-NI), given i.p. 15 min before histami ne-moderately increased the histamine-induced ACTH secretion and did not su bstantially alter the histamine-induced corticosterone secretion. Pretreatm ent with 7-NI totally abolished the HTMT-induced increase in ACTH and corti costerone secretion. The amthamine-evoked rise in ACTH secretion was modera tely diminished and the amthamine-induced corticosterone secretion was not substantially altered by preatreatment with 7-NI. These results suggest tha t the histamine H-receptor transmited central stimulation of the HPA axis i s considerably mediated by endogenous NO, whereas stimulation by histamine and via H-2-receptor does not significantly depend on endogenous NO mediati on.