Studies of Nitric Oxide Generation from Salivary Nitrite in Human Gastric Juice

Background: Saliva contains substantial concentrations of nitrite derived from the enterosalivary recirculation of dietary nitrate. Methods: We have investigated factors in gastric juice influencing the fate of nitrite in swallowed saliva. When nitrite (100 μM) is added to human gastric juice pH 1.5 or pH 2.5 at 37 °C containing physiological concentrations of thiocyanate (1 mM) and ascorbic acid (200 μM), it is converted to nitric oxide within a few seconds. Results: The reduction of nitrite to nitric oxide is slower at pH 3.5 and very little is generated at pH 4.5. The rate of nitric oxide generation at acid pH increases with increasing thiocyanate concentration. The concentration of nitric oxide generated in the above way is maintained until the ascorbic acid is depleted by the recycling of nitric oxide to nitrite. In gastric juice depleted of ascorbic acid, very little nitrite is reduced to nitric oxide at any pH. Conclusion: These studies indicate that in the healthy acid-secreting stomach most salivary nitrite will be reduced to nitric oxide at the gastro-oesophageal junction and gastric cardia where it first encounters gastric juice.