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−1·min−1, respectively, while NaNO2 (12 mM) released NO at a rate of 0.06 nmol·mL−1·min−1 and 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.
Highlights
In mammalian cells nitric oxide (NO) is synthesized by NO synthases (NOS) from L-arginine, and it mediates several biological processes, including neurotransmission, vasodilation, host defense and immunity [1]
Cyclooxygenase inhibition in the gastrointestinal mucosa by nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with gastric mucosal blood flow (GMBF) alterations, which leads to gastrointestinal injury as a common
We evaluated the effect of luminal SNAC solution administration on Sprague Dawley rat GMBF compared to the effects of sodium nitrite (NaNO2) and sodium nitrate (NaNO3) solutions at pH 7.4 using Laser Doppler Flowmetry
Summary
In mammalian cells nitric oxide (NO) is synthesized by NO synthases (NOS) from L-arginine, and it mediates several biological processes, including neurotransmission, vasodilation, host defense and immunity [1]. NO-mediated vasodilation is a fundamental gastric mucosa defense mechanism, as impaired blood supply to the stomach renders the mucosa more susceptible to acid and pepsin-induced injuries [2]. NO donor moieties are chemically attached to allow for local NO release in the stomach. This gastric mucosal blood flow regulation by combining NSAIDs with local NO release proved to be a valid and efficacious approach to prevent NSAID-induced gastric lesions [10]. As new modified NSAID development requires novel synthetic routes and clinical trials, an alternative approach is the development of formulations, which combine standard oral NSAIDs with an NO donor drug in a physical mixture
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