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 synthasedeficient 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 diclofenacand 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;51 chromium-labeled EDTA clearance; nitrite; rats; endothelial nitric oxide synthase deficient; gastric mucus THE ROLE OF NITRATE IN OUR diet has been a subject of great controversy over the years. The anxiety concerning nitrate consumption is related to the presumed association with gastrointestinal cancer. Today, however, there are more studies contradicting than supporting such a correlation (36). Several recent studies have in fact suggested that dietary nitrate has a gastroprotective role (6,16,31,32,35,38). Most of the nitrate in our diet originates from green leafy vegetables, a natural source of food for humans. Bacteria in the oral cavity reduce parts of the nitrate to nitrite, and human saliva therefore contains both of these anions (49). A large amount of nitric oxide (NO) is produced in the upper gut when swallowed nitrite reacts with hydrogen ions (6,35,37).

Identification of Galectin-2–Mucin Interaction and Possible Formation of a High Molecular Weight Lattice

“…23,24) Large quantities of NO are known to be generated in the stomach by the non-enzymatic acid reduction of salivary nitrite, in addition to the NO generated enzymatically by NO synthase from L-arginine, and have been proposed to exert various physiological functions in the gastrointestinal tract [35][36][37][38] including as a barrier in the stomach. [39][40][41] Therefore, it is possible that the NO generated in the stomach Snitrosylates Gal-2 to sustain a stronger barrier through the crosslinking of mucins and to prevent the oxidative inactivation of Gal-2.…”

Therapeutic Uses of Inorganic Nitrite and Nitrate

“…105,106 The reasons for these rare complications (which disappeared on discontinuation of nitrate therapy in most cases) remain unclear but may have been due to contamination of the nitrate salt with nitrite, renal insufficiency causing elevated circulating levels of nitrate, or gastrointestinal disorders with enhanced reduction of nitrate to nitrite by the bacterial gut flora. 107 With alternative diuretics in the form of organic mercurials available, the therapeutic use of nitrates as diuretics was abandoned by the mid-1930s.…”

Nitrate and Nitrite Content of Human, Formula, Bovine, and Soy Milks: Implications for Dietary Nitrite and Nitrate Recommendations

“…11 In humans, dietary nitrate and nitrite sources have been demonstrated to lower blood pressure [12][13][14] and decrease oxygen consumption during submaximal and maximal aerobic exercise. 15,16 In animal models, nitrite has been demonstrated to enhance mucosal blood flow and serve antimicrobial functions, 17 protect against heart attack 18 and stroke, 19 and reverse vascular inflammation from a high fat diet. 20 Gastroprotective and blood pressure-lowering effects of dietary nitrate are abolished by frequent spitting after nitrate consumption or by antiseptic mouthwash.…”