Effect of exogenous nitric oxide and inhibitors of nitric oxide synthase on the hypothalamic pituitary adrenal axis responses to neural stimuli.
It has been shown that the hypothalamic-pituitary-adrenal (HPA) axis responses to immune-derived stimuli in particular can be modulated by nitric oxide (NO). In the present study we examined the effect of endogenous and exogenous NO on the HPA axis responses to neural stimuli which are not related to immune functions. Intracerebroventricular injection of NOR-3, a donor of 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-dependent manner. Intracerebroventricular administration of N-omega-nitro-L-arginine methyl ester (L-NAME), a general NOS inhibitor, significantly enhanced 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, an 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 effect is probably mediated by neuronal NOS and not by inducible NOS.
Weidenfeld
J
J
Department of Neurology, Bikur Cholim Hospital, Jerusalem, Israel.
Feldman
S
S
DeKeyser
F G
FG
Ovadia
H
H
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000201:enzymology*; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein; D007813:Laparotomy; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009574:Nitro Compounds / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D012795:Sialoglycoproteins / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism
D018501:Antirheumatic Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D053590:Interleukin 1 Receptor Antagonist Protein; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D012795:Sialoglycoproteins; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C061872:FK 409; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester