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

The reversible redox conversion of nitrite and nitric oxide ((NO)-N-center dot) in a physiological setting is now widely accepted. Nitrite has long been identified as a stable intermediate of (NO)-N-center dot 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)-N-center dot in the stomach. Once formed, (NO)-N-center dot 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)-N-center dot 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)-N-center dot and dietary compounds, such as glutamate). The redox interplay of nitrite and (NO)-N-center dot 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)-N-center dot-mediated process. We here discuss the implications of the redox conversion of nitrite to (NO)-N-center dot in the gut, how nitritederived (NO)-N-center dot 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. (C) 2013 The Authors. Published by Elsevier B.V. Open access under CC BY-N -N license.