EFFECTS OF CARBON-MONOXIDE ON THE BRAIN MAY BE MEDIATED BY NITRIC-OXIDE

Carbon monoxide (GO) is known to be a toxic molecule due to the high a ffinity of hemoglobin for it. However, it has recently been shown that low doses of CO may play a physiological role. The aim of the present study was to examine processes occurring in the brain during exposure to 1,000 parts per million CO that result in an increase in cerebral blood flow (CBF) but. are not accompanied by changes in oxidative meta bolism This study was carried out in awake rats with the multiprobe as sembly developed in this laboratory for the simultaneous continuous me asurement of CBF, intramitochondrial NADH redox levels, direct current potential, and extracellular concentrations of K+, Ca2+, and H+ as we ll as the electrocorticogram. Exposure to 1,000 parts per million CO i n air resulted in an increased CBF without any concomitant changes in any of the other metabolic or ionic parameters measured. This indicate s that tissue hypoxia was not the trigger for this vasodilation. Injec tion of N-omega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhi bitor, before exposure to CO effectively blocked the increase in CBF t hat was observed when the animal was exposed to CO without prior injec tion of L-NNA. Furthermore, electrocorticographic depression was obser ved after the combined treatment of L-NNA and CO. In conclusion, expos ure to relatively low doses of CO apparently does not have a deleterio us effect on oxidative metabolism because the increase in CBF after th is exposure is sufficient to prevent changes in oxidative metabolism, as indicated by the fact that NADH levels remained constant. This prot ective autoregulatory effect may be mediated by nitric oxide.