Characterization of suppression of nitric oxide production by carbon monoxide poisoning in the striatum of free-moving rats, as determined by in vivo brain microdialysis

Abstract

We examined the effect of carbon monoxide (CO) poisoning on the nitric oxide (NO) system in the striatum of free-moving rats by means of in vivo brain microdialysis. The extracellular levels of the oxidative NO products, nitrite (NO 2 −) and nitrate (NO 3 −), decreased during exposure to CO at 3000 ppm for 40 min, a condition which causes CO poisoning. The extracellular levels of citrulline (Cit; a by-product of NO production) and arginine (Arg; an NO precursor) also decreased during CO exposure. Following reoxygenation by withdrawal of CO, the NO 2 − and NO 3 − levels gradually recovered to the control values, though Arg and Cit remained at lower levels, except for a rapid, but transient, recovery shortly before and after reoxygenation, respectively. Simultaneous application of exogenous l-Arg (50 and 100 mM) with CO exposure attenuated the decreases in NO 2 − and NO 3 − during the CO exposure and accelerated their recovery following reoxygenation. However, d-Arg (100 mM) had no effect on the decrease in NO 2 − and NO 3 −, except for slight and transient attenuation shortly after reoxygenation. Exogenous l-Cit (10 and 100 mM) failed to attenuate the CO-induced decrease in NO 2 − and NO 3 − levels. The decrease in the NO 2 − and NO 3 − levels during 8% O 2 exposure for 40 min, which was comparable with that in response to 3000 ppm CO, was resistant to exogenous 100 mM l-Arg, but the recovery of the NO 2 − and NO 3 − levels following reoxygenation was strongly accelerated. These findings suggest that CO poisoning suppresses NO production in rat striatum in vivo though a mechanism which may not be common with that in hypoxic hypoxia.