The Roles of Carbon Monoxide and Nitric Oxide in the Control of the Neuroendocrine Stress Response: Complementary or Redundant

Abstract

There is widespread evidence in favour of nitric oxide (NO) acting as a gaseous neurotransmitter in the central nervous system, diffusing from its cells of origin and affecting surrounding neuronal tissue in evanescent three-dimensional waves. This is also true of the hypothalamus, where amongst other activities NO inhibits stimulation of corticotrophin-releasing hormone (CRH) and vasopressin release by inflammatory stressors, effects thought to be mediated by binding with soluble guanylate cyclase (sGC). Carbon monoxide is being increasingly recognised as another gaseous neuromodulator, but with principal effects on other hemoproteins such as cyclo-oxygenase, and a distinctly different profile of localisation. NO is predominantly a pro-inflammatory agent in the periphery while CO is often anti-inflammatory. In the hypothalamus, the actions of CO are also distinct from those of NO, with marked antagonistic effects on the inflammatory release of vasopressin, both in vitro and in vivo, but with little involvement in the regulation of CRH. Thus, it would appear that these apparently similar gases exert quite distinct and separate effects, although they cause broadly similar overall changes in the secretion of neuroendocrine stress hormones. We conclude that that these two gases may play significant but different roles in the control of the neuroendocrine stress response, but one common feature may be attenuation of inflammation-induced release of stress hormones.