Adult male rats exposed to an alcohol diet exhibit a blunted adrenocorticotropic hormone response to immune or physical stress: possible role of nitric oxide.
Intact adult male rats fed an alcohol [ethanol (EtOH)] diet for 10 days show blunted adrenocorticotropic hormone (ACTH) release in response to immune signals such as the cytokine interleukin-1 beta (IL-1 beta) and endotoxin [lipopolysaccharide (LPS)], as well as to physical stress (mild electroshocks). The mechanisms responsible for this effect remain poorly understood, but we have recently reported that decreased pituitary responsiveness to vasopressin (VP) might play a role. In naive rats, nitric oxide (NO) exerts a restraining influence on the response of the hypothalamic-pituitary (H-P) axis to cytokines and VP. The ability of long-term EtOH treatment to increase glutamate receptors, and thus NO formation, prompted us to test the hypothesis that abnormally high NO concentrations might modulate the influence of the drug. Blockade of the activity of NO synthase (NOS), the enzyme responsible for NO formation, with the arginine derivative L-N omega nitro-L-arginine-methylester (L-NAME), augmented the ACTH response to IL-1 beta or LPS in both control (C) and EtOH-fed (E) rats. Indeed, after L-NAME treatment, ACTH concentrations were statistically comparable in C and E animals injected with endotoxin or a large dose of IL-1 beta. VP-induced ACTH secretion also became comparable in both experimental groups after blockade of NOS activity. In contrast, the decreased response of the H-P axis of E animals to shocks was only slightly ameliorated, compared with that of C rats. It is therefore possible that changes in the NOergic tone induced by alcohol play a role in the decreased response of the H-P axis to cytokines, possibly in part by altering the stimulatory action of VP on the corticotrophs. On the other hand, in E rats NO seems to exert only a minimal influence on the central nervous system circuits activated by shocks.
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Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037, USA.
D000302:Adrenal Cortex / Q000187:drug effects / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D000431:Ethanol / Q000633:toxicity; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007375:Interleukin-1 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D013312:Stress, Physiological / Q000503:physiopathology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D017470:Receptors, Glutamate; D009569:Nitric Oxide; D000431:Ethanol; D000324:Adrenocorticotropic Hormone