title: Dietary nitrate increases gastric mucosal blood flow and mucosal defense.
abstract: 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 ((51)Cr-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.
authors.affiliation: Medical Cell Biology, Uppsala University, Uppsala, Sweden. joel.petersson@medcellbiol.uu.se
authors.forename: Joel
authors.initials: J
authors.lastname: Petersson
authors.forename: Mia
authors.initials: M
authors.lastname: Phillipson
authors.forename: Emmelie A
authors.initials: EA
authors.lastname: Jansson
authors.forename: Andreas
authors.initials: A
authors.lastname: Patzak
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.forename: Lena
authors.initials: L
authors.lastname: Holm
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013270:Stomach / Q000187:drug effects; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D009566:Nitrates; D009573:Nitrites; D004008:Diclofenac; D009569:Nitric Oxide; D013656:Taurocholic Acid; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse