Effect of exogenous nitric oxide and inhibitors of nitric oxide synthase on the hypothalamic pituitary adrenal axis responses to neural stimuli

It has been sh own that the hypothalamic-pituitary-ad renal (HPA) axis resp onses to immune-derived stimuli in particular can be modulated by nitric ox ide (NO). In the present study we examined the effect of endogenous and exo genous NO on the HPA axis responses to neural stimuli which are not related to immune functions. Intracerebroventricular injection of NOR-3, a donor o f NO, had no effect on basal HPA axis activity but significantly attenuated the secretion of median eminence (ME) CRH-41 as well as the serum ACTH and corticosterone (CS) in response to acute photic stimulation in a dose-depe ndent manner. Intracerebroventricular administration of N-omega-nitro-L-arg inine methyl ester (L-NAME), a general NOS inhibitor, significantly enhance d ACTH and CS responses to this stress but did not change the basal levels of these hormones. On the other hand, i.c.v. injection of aminoguanidine, a n inhibitor of inducible NO synthase (NOS) but not of neuronal NOS, did not affect the HPA axis responses to photic stimulation. These results suggest that: (1) NO is involved in modulation of the HPA axis responses to neural stimuli which are not dependent on immune factors, (2) the effect of NO is mediated by inhibition of hypothalamic ME CRH-41 secretion, and (3) this e ffect is probably mediated by neuronal NOS and not by inducible NOS.