INFLUENCE OF CARBON-MONOXIDE, AND ITS INTERACTION WITH NITRIC-OXIDE, ON THE ADRENOCORTICOTROPIN HORMONE RESPONSE OF THE NORMAL RAT TO A PHYSICO-EMOTIONAL STRESS

We determined whether the gas carbon monoxide (CO) altered the adrenoc orticotropin hormone (ACTH) response to mild inescapable electrofootsh ocks, and whether it interacted with nitric oxide (NO). Peripheral inj ection of the NO synthase (NOS) inhibitor Nwnitro-L-arginine-methylest er (L-NAME), a compound which readily crosses the blood-brain barrier, produced the expected blunting of the ACTH response to the shocks. Th is effect was mimicked by other arginine analogues such as L-nitroargi nine (L-NNA) and N-G-methyl-L-arginine (NMMA), The subcutaneous (s.c.) administration of the heme oxygenase (HO) blockers tin mesoporphyrin (SnMP) or tin protoporphyrin (SnPP) significantly decreased brain HO l evels, indicating that both compounds had penetrated the brain. Blood pressure showed a modest increase in response to SnMP, and no change a fter SnPP. SnMP and SnPP both decreased shock-induced ACTH release, th ough the magnitude of this effect was slightly less than that of L-NAM E, The influence of SnPP was further augmented in rats with concomitan t blockade of NO formation, which suggests that both NO and CO are nec essary for the full response of this axis to electrofootshocks, Finall y, the ability of SnPP to significantly blunt the expression of the mR NA for the immediate early gene NGFI-B in the paraventricular nucleus (PVN) of rats exposed to shocks, indicates that the influence of CO wa s exerted on hypothalamic neuronal activity. Collectively, our results show that NO and CO exert a stimulatory effect on the HPA axis respon se to mild electrofootshocks, and that at least part of this influence takes place on hypothalamic neurons and/or their afferents.