Nitric Oxide Released from Luminal S-Nitroso-N-Acetylcysteine Increases Gastric Mucosal Blood Flow

Abstract

Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal defense, and NO-donor drugs may protect against diseases associated with gastric mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo gastric chamber method and Laser Doppler Flowmetry to characterize the effects of luminal aqueous NO-donor drug S-nitroso-N-acetylcysteine (SNAC) solution administration compared to aqueous NaNO2 and NaNO3 solutions (pH 7.4) on GMBF in Sprague-Dawley rats. SNAC solutions (600 μM and 12 mM) led to a rapid threefold increase in GMBF, which was maintained during the incubation of the solutions with the gastric mucosa, while NaNO2 or NaNO3 solutions (12 mM) did not affect GMBF. SNAC solutions (600 μM and 12 mM) spontaneously released NO at 37 °C at a constant rate of 0.3 or 14 nmol·mL, respectively, while NaNO2 (12 mM) released NO at a rate of 0.06 nmol·mLand NaNO3 (12 mM) did not release NO. These results suggest that the SNAC-induced GMBF increase is due to their higher rates of spontaneous NO release compared to equimolar NaNO2 solutions. Taken together, our data indicate that oral SNAC administration is a potential approach for gastric acid-peptic disorder prevention and treatment.

Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases

“…Through transnitrosation, new S-nitrosothiols and thiols can be generated and activate biological functions [ 94 ]. For example, S-nitrosothiols play a role in gastric mucosal defense, potentially preserving the integrity of the stomach lining and providing protection against damage induced by ROS or other harmful agents [ 95 , 96 ].…”