The nitric oxide/ascorbate cycle: how neurones may control their own oxygen supply

The brain requires an extremely precise means of controlling oxygen delivery to neurones. Too much, and the cells risk free-radical-mediated damage: too little, and the neurones die from hypoxic-excitotoxic mechanisms. Although nitric oxide (NO) is a powerful vasodilator in cerebral blood vessels, synthesis of NO from arginine requires oxygen and so is unsuitable as the mediator of hypoxia-induced cerebral vasodilation. This paper describes a model in which ascorbate, released from neurones during activity, generates NO from the reduction of nitrite ions in the extracellular space. This mechanism could subtly and accurately match the oxygen transport to the local metabolic demands of the nerve cells. The model predicts that the consequences of low ascorbate in the brain would be progressive damage from inaccurate oxygen delivery.