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Am J Physiol Gastrointest Liver Physiol 292: G718-G724, 2007. First published November 2, 2006; doi:10.1152/ajpgi.00435.2006
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MUCOSAL BIOLOGY

Dietary nitrate increases gastric mucosal blood flow and mucosal defense

Joel Petersson,1 Mia Phillipson,1 Emmelie Å. Jansson,2 Andreas Patzak,3 Jon O. Lundberg,2 and Lena Holm1

1Medical Cell Biology, Uppsala University, Uppsala, Sweden; 2Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; and 3Johannes-Müller-Institute of Physiology, Humboldt University, Berlin, and University Hospital Charité, Berlin, Germany

Submitted 21 September 2006 ; accepted in final form 31 October 2006

Salivary nitrate from dietary or endogenous sources is reduced to nitrite by oral bacteria. In the acidic stomach, nitrite is further reduced to bioactive nitrogen oxides, including nitric oxide (NO). In this study, we investigated the gastroprotective role of nitrate intake and of luminally applied nitrite against provocation with diclofenac and taurocholate. Mucosal permeability (51Cr-EDTA clearance) and gastric mucosal blood flow (laser-Doppler flowmetry) were measured in anesthetized rats, either pretreated with nitrate in the drinking water or given acidified nitrite luminally. Diclofenac was given intravenously and taurocholate luminally to challenge the gastric mucosa. Luminal NO content and nitrite content in the gastric mucus were determined by chemiluminescence. The effect of luminal administration of acidified nitrite on the mucosal blood flow was also investigated in endothelial nitric oxide synthase-deficient mice. Rats pretreated with nitrate or given nitrite luminally had higher gastric mucosal blood flow than controls. Permeability increased more during the provocation in the controls than in the nitrate- and nitrite-treated animals. Dietary nitrate increased luminal NO levels 50 times compared with controls. Nitrate intake also resulted in nitrite accumulation in the loosely adherent mucous layer; after removal of this mucous layer, blood flow was reduced. Nitrite administrated luminally in endothelial nitric oxide synthase-deficient mice increased mucosal blood flow. We conclude that dietary nitrate and direct luminal application of acidified nitrite decrease diclofenac- and taurocholate-induced mucosal damage. The gastroprotective effect likely involves a higher mucosal blood flow caused by nonenzymatic NO production. These data suggest an important physiological role of nitrate in the diet.

laser-Doppler flowmetry; 51chromium-labeled EDTA clearance; nitrite; rats; endothelial nitric oxide synthase deficient; gastric mucus



Address for reprint requests and other correspondence: J. Petersson, Dept. of Medical Cell Biology, Uppsala Univ., Husargatan 3, BMC B1:2, S-751 23 Uppsala, Sweden (e-mail: joel.petersson{at}medcellbiol.uu.se)




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