Nitric oxide mediated neurovascular coupling is maintained under hypoxia through ascorbate-dependent nitrite reduction to NO: An in vivo study in the hippocampus

The brain has a very high energetic demand requiring a constant supply of O 2 and glucose. Coping with these requirements implies that only a restricted number of neuronal cells fire simultaneously and their metabolic needs are satisfied through the local and transient increase in cerebral blood flow (CBF) via the mechanism of neurovascular coupling (NYC), in a process mediated by • NO. However, when O 2 supply is diminished, this pathway for NYC is impaired. In this work we tested the hypothesis that under hypoxic conditions nitrite is a source of • NO in the brain, through its reduction by ascorbate. For that, we used an in vivo approach to monitor • NO and CBF dynamics in the hippocampus, involving the insertion of selective microelectrodes and arrays. Results show that the local microinjection of nitrite in animals submitted to short-term hypercapnia induced a transient increase of • NO in the nM range, concomitantly with transient increases in CBF. Furthermore, it was observed a decrease in extracellular levels of ascorbate timely coupled with the production of • NO. Results suggest that reduction of nitrite to • NO by ascorbate occurs in the brain, thus constituting a pathway for • NO mediated NYC when nNOS function is impaired due to limited availability of O 2 .