title: Diffusion of nitric oxide through the gastric wall upon reduction of nitrite by red wine: physiological impact.
abstract: 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 microM range (>100 microM) in the serosal side. In order to evaluate whether cellular dysfunction was associated with *NO diffusion at the microM 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 microM 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.
authors.affiliation: Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Bárbara S
authors.initials: BS
authors.lastname: Rocha
authors.forename: Bruno
authors.initials: B
authors.lastname: Gago
authors.forename: Rui M
authors.initials: RM
authors.lastname: Barbosa
authors.forename: João
authors.initials: J
authors.lastname: Laranjinha
mesh_terms: D000818:Animals; D004058:Diffusion; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D009573:Nitrites / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014920:Wine / Q000032:analysis*
chemical_list: D009573:Nitrites; D009569:Nitric Oxide