Role of Blood Flow in Gastric and Duodenal Mucosal Injury in the Rat

Leung, Felix W.; Itoh, Makoto; Hirabayashi, Ken; Guth, Paul H.

doi:10.1016/s0016-5085(85)80181-5

Cited by 140 publications

(35 citation statements)

References 21 publications

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“…This injury was confined to the very superficial mucosa (type 1 damage) and consisted of surface mucous cell damage and areas of vasocongestion. These findings are in agreement with those previously reported (Leung et al, 1985) in a model of experimental damage following haemorrhagic shock plus intragastric HCl, where only mild damage was observed when the reduction in blood pressure and mucosal blood flow was less than 30-40%. In that study, systemic blood pressure and mucosal blood flow had to be reduced to 25% or less of the baseline value before severe and extensive lesions appeared.…”

Section: Discussionsupporting

confidence: 93%

“…Gastric damage has also been documented experimentally with endotoxin-induced sepsis or septic shock (Cheung et al, 1975). The importance of mucosal blood flow in the defence of the gastric mucosa against injury has been demonstrated in haemorrhagic shock models (Starlinger et al, 1981;Leung et al, 1985). Increased gastric blood flow has been reported in studies using live organisms to induce bacteriaemia (Nilsson et al, 1983;Genter et al, 1983), but a decreased gastric blood flow has been reported with intra-arterial infusion of endotoxin even in the absence of systemic hypotension (Cheung et al, 1976).…”

Section: Discussionmentioning

confidence: 99%

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Indomethacin potentiates endotoxin‐induced blood flow reduction and histological injury in rat gastric mucosa

Piqué¹,

Yasuda²,

Whittle³

et al. 1988

British J Pharmacology

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Indomethacin potentiates endotoxin‐induced blood flow reduction and histological injury in rat gastric mucosa

Piqué¹,

Yasuda²,

Whittle³

et al. 1988

British J Pharmacology

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“…To withstand this constantly changing challenge it is of paramount importance that the mucosal defense systems can adapt instantly. Among these defense mechanisms, mucosal blood flow and mucus secretion play central roles (1)(2)(3)(4)(5)(6)(7). A rapid increase in mucosal blood flow following exposure to a luminal irritant allows for buffering of acid and removal of toxic compounds.…”

Section: Introductionmentioning

confidence: 99%

Nitrite in saliva increases gastric mucosal blood flow and mucus thickness

Björne¹,

Petersson²,

Phillipson³

et al. 2004

J. Clin. Invest.

207

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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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“…Numerous experimental studies have demonstrated the importance of mucosal blood flow in the defense of the gastric mucosa against injury (1,12,20,27,33,42,47,52). The blood flow carries bicarbonate to neutralize acid and removes cellular waste products.…”

mentioning

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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Role of Blood Flow in Gastric and Duodenal Mucosal Injury in the Rat

Cited by 140 publications

References 21 publications

Indomethacin potentiates endotoxin‐induced blood flow reduction and histological injury in rat gastric mucosa

Indomethacin potentiates endotoxin‐induced blood flow reduction and histological injury in rat gastric mucosa

Nitrite in saliva increases gastric mucosal blood flow and mucus thickness

Dietary nitrate increases gastric mucosal blood flow and mucosal defense

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