The redox interplay between nitrite and nitric oxide: From the gut to the brain

• Dietary nitrite converts to NO in the gut, triggering the modification of proteins and lipids.
• Polyphenols and ascorbate facilitate the redox conversion of nitrite to NO in the stomach.
• Dietary nitrite-derived NO triggers physiological responses.
• The nitrite: NO: ascorbate interplay in brain may impact functionally upon glutamatergic stimulation.

The reversible redox conversion of nitrite and nitric oxide (NO) in a physiological setting is now widely accepted. Nitrite has long been identified as a stable intermediate of NO oxidation but several lines of evidence support the reduction of nitrite to nitric oxide in vivo. In the gut, this notion implies that nitrate from dietary sources fuels the longstanding production of nitrite in the oral cavity followed by univalent reduction to NO in the stomach. Once formed, NO boosts a network of reactions, including the production of higher nitrogen oxides that may have a physiological impact via the post-translational modification of proteins and lipids. Dietary compounds, such as polyphenols, and different prandial states (secreting specific gastric mediators) modulate the outcome of these reactions. The gut has unusual characteristics that modulate nitrite and NO redox interplay: (1) wide range of pH (neutral vs acidic) and oxygen tension (c.a. 70 Torr in the stomach and nearly anoxic in the colon), (2) variable lumen content and (3) highly developed enteric nervous system (sensitive to NO and dietary compounds, such as glutamate). The redox interplay of nitrite and NO might also participate in the regulation of brain homeostasis upon neuronal glutamatergic stimulation in a process facilitated by ascorbate and a localized and transient decrease of oxygen tension. In a way reminiscent of that occurring in the stomach, a nitrite/NO/ascorbate redox interplay in the brain at glutamatergic synapses, contributing to local NO increase, may impact on NO-mediated process.We here discuss the implications of the redox conversion of nitrite to NO in the gut, how nitrite-derived NO may signal from the digestive to the central nervous system, influencing brain function, as well as a putative ascorbate-driven nitrite/NO pathway occurring in the brain.