Diffusion of nitric oxide through the gastric wall upon reduction of nitrite by red wine: Physiological impact

In this work we showed that nitric oxide produced via red wine- and ascorbate-dependent reduction of nitrite diffuses through the rat stomach, inducing smooth muscle relaxation. The studies encompassed ex vivo and in vivo models of diffusion. Regarding the former, luminal NO generated from a mixture of physiologic nitrite and ascorbate or wine diffuses across the stomach wall, being 8–20% of that produced in the mucosal side detected at high μM range (>100 μM) in the serosal side. In order to evaluate whether cellular dysfunction was associated with NO diffusion at the μM range, the gastric tissue exposed to NO was evaluated in terms of carbachol-induced muscle contraction in fundal strips and mitochondrial respiration and showed to remain functional and metabolically active. Moreover, pre-contracted gastric strips were shown to relax 86.5 ± 5.5% (control) and 75.0 ± 4.0% (nitrite/ascorbate-exposed tissue) when challenged with acidified nitrite. The studies in the living animal support the diffusion of luminal NO to the gastric vasculature as, following addition of nitrite/ascorbate to rat stomach in vivo, NO was not detected in the serosal environment but concentrations as high as 31 μM of NO were detected outside the stomach after cardiac arrest. Collectively, the results establish a link between the consumption of nitrite and dietary reductants (e.g., wine polyphenols) and stomach muscle relaxation via the local chemical generation of NO.