Rat gastric mucosal microcirculation in vivo

Holm-Rutili, Lena; Öbrink, Karl Johan

doi:10.1152/ajpgi.1985.248.6.g741

Cited by 30 publications

(21 citation statements)

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“…The gastric preparation for blood flow and mucus thickness measurements has been described previously in detail (15,30). In brief, the abdomen was opened through a midline incision and the stomach was gently exteriorized.…”

Section: Methodsmentioning

confidence: 99%

Nitrite in saliva increases gastric mucosal blood flow and mucus thickness

Björne¹,

Petersson²,

Phillipson³

et al. 2004

J. Clin. Invest.

208

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Salivary nitrate from dietary or endogenous sources is reduced to nitrite by oral bacteria. In the acidic stomach, nitrite is further reduced to NO and related compounds, which have potential biological activity. We used an in vivo rat model as a bioassay to test effects of human saliva on gastric mucosal blood flow and mucus thickness. Gastric mucosal blood flow and mucus thickness were measured after topical administration of human saliva in HCl. The saliva was collected either after fasting (low in nitrite) or after ingestion of sodium nitrate (high in nitrite). In additional experiments, saliva was exchanged for sodium nitrite at different doses. Mucosal blood flow was increased after luminal application of nitrite-rich saliva, whereas fasting saliva had no effects. Also, mucus thickness increased in response to nitrite-rich saliva. The effects of nitrite-rich saliva were similar to those of topically applied sodium nitrite. Nitrite-mediated effects were associated with generation of NO and S-nitrosothiols. In addition, pretreatment with an inhibitor of guanylyl cyclase markedly inhibited nitrite-mediated effects on blood flow. We conclude that nitrite-containing human saliva given luminally increases gastric mucosal blood flow and mucus thickness in the rat. These effects are likely mediated through nonenzymatic generation of NO via activation of guanylyl cyclase. This supports a gastroprotective role of salivary nitrate/nitrite.

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Section: Methodsmentioning

confidence: 99%

Nitrite in saliva increases gastric mucosal blood flow and mucus thickness

Björne¹,

Petersson²,

Phillipson³

et al. 2004

J. Clin. Invest.

208

View full text Add to dashboard Cite

show abstract

“…The gastric preparation for in vivo microscopy has previously been described in detail (12,15). Briefly, exteriorization of the stomach through a midline abdominal incision was followed by an incision along the greater curvature in the forestomach.…”

Section: Animal Preparationmentioning

confidence: 99%

The gastric mucus layers: constituents and regulation of accumulation

Phillipson¹,

Johansson²,

Henriksnäs³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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The mucus layer continuously covering the gastric mucosa consists of a loosely adherent layer that can be easily removed by suction, leaving a firmly adherent mucus layer attached to the epithelium. These two layers exhibit different gastroprotective roles; therefore, individual regulation of thickness and mucin composition were studied. Mucus thickness was measured in vivo with micropipettes in anesthetized mice [isoflurane; C57BL/6, Muc1−/−, inducible nitric oxide synthase (iNOS)−/−, and neuronal NOS (nNOS)−/−] and rats (inactin) after surgical exposure of the gastric mucosa. The two mucus layers covering the gastric mucosa were differently regulated. Luminal administration of PGE2increased the thickness of both layers, whereas luminal NO stimulated only firmly adherent mucus accumulation. A new gastroprotective role for iNOS was indicated since iNOS-deficient mice had thinner firmly adherent mucus layers and a lower mucus accumulation rate, whereas nNOS did not appear to be involved in mucus secretion. Downregulation of gastric mucus accumulation was observed in Muc1−/− mice. Both the firmly and loosely adherent mucus layers consisted of Muc5ac mucins. In conclusion, this study showed that, even though both the two mucus layers covering the gastric mucosa consist of Muc5ac, they are differently regulated by luminal PGE2and NO. A new gastroprotective role for iNOS was indicated since iNOS−/− mice had a thinner firmly adherent mucus layer. In addition, a regulatory role of Muc1 was demonstrated since downregulation of gastric mucus accumulation was observed in Muc1−/− mice.

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“…The chamber was filled with warm (37°C) unbuffered 0.9% saline solution to keep the tissue moist and prevent the mucous gel from dehydration. The technique has been described in detail previously (23,26).…”

Section: Tissue Preparationmentioning

confidence: 99%

Dietary nitrate increases gastric mucosal blood flow and mucosal defense

Petersson

Phillipson²,

Jansson³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

130

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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).

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Rat gastric mucosal microcirculation in vivo

Cited by 30 publications

References 0 publications

Nitrite in saliva increases gastric mucosal blood flow and mucus thickness

Nitrite in saliva increases gastric mucosal blood flow and mucus thickness

The gastric mucus layers: constituents and regulation of accumulation

Dietary nitrate increases gastric mucosal blood flow and mucosal defense

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