Effect of nitrite on the electroencephalographic activity in the healthy brain

Background: Nitrite is a major intravascular store for nitric oxide. The conversion of nitrite to the active nitric oxide occurs mainly under hypoxic conditions to increase blood flow where it is needed the most. The use of nitrite is, therefore, being evaluated widely to reduce the brain injury in conditions resulting in cerebral hypoxia, such as cardiac arrest, ischaemic stroke or subarachnoid haemorrhage. However, as it is still unknown how exogenous nitrite affects the brain activity of healthy individuals, it is difficult to clearly understand how it affects the ischaemic brain. Objective: Here we performed a double-blind placebo-controlled crossover study to investigate the effects of nitrite on neural activity in the healthy brain. Methods: Twenty-one healthy volunteers were recruited into the study. All participants received a continuous infusion of sodium nitrite (0.6 mg/kg/h) on one occasion and placebo (sodium chloride) on another occasion. Electroencephalogram was recorded before the start and during the infusion. We computed the power spectrum density within the conventional frequency bands (delta, theta, alpha, beta), and the ratio of the power within the alpha and delta bands. We also measured peripheral cardiorespiratory physiology and cerebral blood flow velocities. Results: We found no significant effect of nitrite on the power spectrum density in any frequency band. Similarly, the alpha-delta power ratio did not differ between the two conditions. The peripheral cardiorespiratory physiology and middle cerebral artery velocity and associated indices were also unaffected by the nitrite infusion. However, nitrite infusion decreased the mean blood pressure and increased the methaemoglobin concentration in the blood. Conclusion: Our study shows that exogenous sodium nitrite does not alter the electrical activity in the healthy brain. This might be because the sodium nitrite is converted to vasoactive nitric oxide in areas of hypoxia, and in the healthy brain there is no significant amount of conversion due to lack of hypoxia. However, this lack of change in the power spectrum density in healthy people emphasises the specificity of the brain's response to nitrite in disease.