Red wine-dependent reduction of nitrite to nitric oxide in the stomach

Nitrite may be a source for nitric oxide (*NO), particularly in highly acidic environments, such as the stomach. Diet products contribute also with reductants that dramatically increase the production of *NO from nitrite. Red wine has been attributed health promoting properties largely on basis of the reductive antioxidant properties of its polyphenolic fraction. We show in vitro that wine, wine anthocyanin fraction and wine catechol (caffeic acid) dose- and pH-dependently promote the formation of *NO when mixed with nitrite, as measured electrochemically. The production of *NO promoted by wine from nitrite was substantiated in vivo in healthy volunteers by measuring *NO in the air expelled from the stomach, following consumption of wine, as measured by chemiluminescence. Mechanistically, the reaction involves the univalent reduction of nitrite, as suggested by the formation of *NO and by the appearance of EPR spectra assigned to wine phenolic radicals. Ascorbic and caffeic acids cooperate in the reduction of nitrite to *NO. Moreover, reduction of nitrite is critically dependent on the phenolic structure and nitro-derivatives of phenols are also formed, as suggested by caffeic acid UV spectral modifications. The reduction of nitrite may reveal previously unrecognized physiologic effects of red wine in connection with *NO bioactivity.