Cerebrovascular effects of carbon monoxide.
This review examines the influence of endogenous and exogenous carbon monoxide (CO) on the cerebral circulation. Although CO generated from neuronal heme oxygenase can modulate neurotransmission, evidence supporting its role in cerebral vasodilation is limited. In newborn piglets, heme oxygenase is enriched in microvessels and contributes to hypoxic vasodilation. Low CO concentrations dilate piglet arterioles by opening calcium-activated potassium channels. With inhalation of CO and formation of carboxyhemoglobin, cerebral vasodilation can be greater than that occurring with hypoxic hypoxia at equivalent reductions of arterial oxygen content. This additional vasodilation is probably attributable to additional release of hypoxic vasodilators secondary to increased oxyhemoglobin affinity, although direct effects of CO on cerebral arterioles may also occur. When CO exposure is prolonged, cerebral endothelium undergoes oxidant stress as evident by nitrotyrosine formation. As CO levels increase, modest decreases in oxygen consumption are detectable, which may reflect CO or nitric oxide interactions with cytochrome oxidase in regions with very low oxygen availability. If subsequent CO concentration increases sufficiently to depress cardiac function and limit cerebral perfusion, cerebral oxygen consumption becomes further reduced, and oxidant stress becomes amplified by leukocyte sequestration and xanthine oxidase activity with consequent lipid peroxidation. Specific regions of the brain, such as central white matter, globus pallidus, and hippocampus, are selectively vulnerable to CO toxicity, but whether the mechanisms involved in selective injury differ from other forms of hypoxia-ischemia needs to be clarified.