The Potent Vasodilator Ethyl Nitrite is Formed Upon Reaction of Nitrite and Ethanol Under Gastric Conditions

By acting as a bioreactor, affording chemical and mechanical conditions for the reaction between dietary components, the stomach may be a source of new bioactive molecules. Using gas chromatography-mass spectrometry we here demonstrate that, under acidic gastric conditions, ethyl nitrite is formed in microM concentrations from the reaction of red wine or distilled alcoholic drinks with physiological amounts of nitrite. Rat femoral artery rings and gastric fundus strips dose-dependently relaxed upon exposure to nitrite:ethanol mixtures. In contrast, when administered separately in the same dose ranges, nitrite evoked only minor vasorelaxation while ethanol actually caused a slight vasoconstriction. Mechanistically, the relaxation effect was assigned to generation of nitric oxide (*NO) as supported by direct demonstration of *NO release from ethyl nitrite and the absence of relaxation in the presence of the soluble guanylyl cyclase inhibitor, ODQ. In conclusion, these results suggest that ethanol in alcoholic drinks interacts with salivary-derived nitrite in the acidic stomach leading to the production of the potent smooth muscle relaxant ethyl nitrite. These findings reveal an alternative chemical reaction pathway for dietary nitrate and nitrite with possible impact on gastric physiology and pathophysiology.