This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, C. K. Articles by Rivier, C. L. Search for Related Content PubMed PubMed Citation Articles by Kim, C. K. Articles by Rivier, C. L.

Nitric Oxide and Carbon Monoxide Have a Stimulatory Role in the Hypothalamic-Pituitary-Adrenal Response to Physico-Emotional Stressors in Rats¹

The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037

Address all correspondence and requests for reprints to: Catherine Rivier, Ph.D., The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037. E-mail: crivier{at}salk.edu

We tested the hypothesis that nitric oxide and carbon monoxide, which are produced in the brain by nitric oxide synthase (NOS) and heme oxygenase (HO), modulate the hypothalamic-pituitary-adrenal response to physico-emotional stressors by acting at the hypothalamus. Accordingly, we determined 1) whether the intracerebroventricular (icv) injection of NOS or HO inhibitors at doses that were confined to the brain attenuated electroshock-induced ACTH release; and 2) whether the decreases in this ACTH response were concurrent with decreases in NOS or HO activity levels at the hypothalamus. Icv injection of the NOS inhibitor N-nitro-L-arginine-methylester (L-NAME; 50 µg) or the HO inhibitor tin protoporphyrin (SnPP; 20–25 µg) significantly blunted the plasma ACTH response to a 45-min session of intermittent electroshocks. Importantly, in these same animals there were concurrent decreases in hypothalamic NOS or HO activities, respectively. There were little or no effects of these inhibitors on anterior pituitary NOS or HO activities, indicating that there was only minimal leakage of the drug from the brain after icv administration. The specificity of action of these inhibitors was confirmed by the fact that SnPP did not affect NOS activity, and L-NAME did not affect HO activity. Finally, L-NAME produced no effect, whereas SnPP produced only transient increases in blood pressure, suggesting that these inhibitors do not affect activity indirectly through alterations in blood pressure. These data support the hypothesis that in the whole animal, both NO and CO exert a stimulatory influence on the acute ACTH response to physico-emotional stressors, and that the hypothalamus is the critical site of their actions.

This article has been cited by other articles:

				C. J McManus, M. Valent, S. L Hardy, and R. L Goodman Does nitric oxide act in the ventromedial preoptic area to mediate oestrogen negative feedback in the seasonally anoestrous ewe? Reproduction, July 1, 2007; 134(1): 137 - 145. [Abstract] [Full Text] [PDF]

				P. M. Jamieson, C. Li, C. Kukura, J. Vaughan, and W. Vale Urocortin 3 Modulates the Neuroendocrine Stress Response and Is Regulated in Rat Amygdala and Hypothalamus by Stress and Glucocorticoids Endocrinology, October 1, 2006; 147(10): 4578 - 4588. [Abstract] [Full Text] [PDF]

				M. Herman and C. Rivier Activation of a Neural Brain-Testicular Pathway Rapidly Lowers Leydig Cell Levels of the Steroidogenic Acute Regulatory Protein and the Peripheral-Type Benzodiazepine Receptor while Increasing Levels of Neuronal Nitric Oxide Synthase Endocrinology, January 1, 2006; 147(1): 624 - 633. [Abstract] [Full Text] [PDF]

				L. Wu and R. Wang Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications Pharmacol. Rev., December 1, 2005; 57(4): 585 - 630. [Abstract] [Full Text] [PDF]

				L. Chen, D. Duricka, S. Nelson, S. Mukherjee, S. G. Bohnet, P. Taishi, J. A. Majde, and J. M. Krueger Influenza virus-induced sleep responses in mice with targeted disruptions in neuronal or inducible nitric oxide synthases J Appl Physiol, July 1, 2004; 97(1): 17 - 28. [Abstract] [Full Text] [PDF]

				C. L. Rivier, D. E. Grigoriadis, and J. E. Rivier Role of Corticotropin-Releasing Factor Receptors Type 1 and 2 in Modulating the Rat Adrenocorticotropin Response to Stressors Endocrinology, June 1, 2003; 144(6): 2396 - 2403. [Abstract] [Full Text] [PDF]

				L. Dufourny and D. C. Skinner Influence of Estradiol on NADPH Diaphorase/Neuronal Nitric Oxide Synthase Activity and Colocalization with Progesterone or Type II Glucocorticoid Receptors in Ovine Hypothalamus Biol Reprod, September 1, 2002; 67(3): 829 - 836. [Abstract] [Full Text] [PDF]

				D. Morse and A. M. K. Choi Heme Oxygenase-1 . The "Emerging Molecule" Has Arrived Am. J. Respir. Cell Mol. Biol., July 1, 2002; 27(1): 8 - 16. [Abstract] [Full Text] [PDF]