Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment 20 min beforehand with an inhibitor of nitric oxide (NO) synthesis NW-nitro-1-arginine methyl ester (L-NAME) (12.5, 25, 50 or 100 mg/kg, s.c.), dose-dependently intensified gastric glandular mucosal ulceration produced by cold-restraint stress. Hexamethonium (20 mg/kg) or atropine (1 mg/kg) pretreatment s.c. 20 min before stress strongly antagonised stress-evoked ulceration, as well as the ulcer-potentiating effects of L-NAME when either cholinoceptor antagonist was given concurrently with the NO inhibitor. Stress-induced mast cell degranulation was not worsened by L-NAME pretreatment. The findings suggest that NO could confer partial protection against stress-induced gastric ulcer formation; its activity is triggered off by the ulcerogenic mechanism of stress.
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PMID:Nitric oxide inhibition intensifies cold-restraint induced gastric ulcers in rats. 809 77

We have reported that endothelin-1 induces gastric ulcer characterized by a potent long-lasting vasoconstriction of the regional microvasculature. Nitric oxide synthesized from L-arginine has been shown to regulated gastric mucosal blood flow, and inhibition of its synthesis has been shown to delay the healing of gastric ulcers. We examined the effect of exogenous L-arginine and the inhibition of nitric oxide synthesis on the development of endothelin-1-induced gastric ulcers. In rats anesthetized with urethane, a continuous intravenous infusion of L- or D-arginine (10 mg.kg-1.min-1) was followed, 15 min later, by a submucosal injection of endothelin-1 (200 pmol/kg) in the anterior wall of the gastric body. In another group, rats were intravenously pretreated with N omega-nitro-L-arginine-methyl ester (1-10 mg/kg), a nitric oxide synthesis inhibitor, and then injected with endothelin-1 (40 pmol/kg). Twenty-four h later, L-arginine, but not D-arginine, had significantly reduced the extent and the severity of the endothelin-1-induced ulcer (mucosal wall damage, 18.11 +/- 4.79% and 88.14 +/- 7.06%, respectively; mean +/- SD, P < 0.001), and the nitric oxide synthesis inhibitor (10 mg/kg) had increased the endothelin-1-induced mucosal damage (ulcer length, 3.8 +/- 1.2 mm and 1.1 +/- 0.2 mm, respectively, P < 0.01). Continuous gastric mucosal blood flow measurements showed that L-arginine antagonized the endothelin-1-induced vasoconstriction. L-arginine protected the gastric mucosa from the ulcerogenic action of endothelin-1 and antagonized its vasoconstrictive action. The inhibition of endogenous nitric oxide potentiated the ulcerogenic effect of endothelin-1 on rat gastric mucosa.
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PMID:L-arginine and endogenous nitric oxide protect the gastric mucosa from endothelin-1-induced gastric ulcers in rats. 857 28

The purpose of this study was to clarify the effect of basic fibroblast growth factor (bFGF) on nitric oxide (NO) synthesis during healing of rat gastric ulcers. After experimental gastric ulcers were induced by acetic acid, rats were treated with vehicle, recombinant human bFGF (CS23, 10 micrograms/kg) and NG-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg), an NO synthase (NOS) inhibitor, through an orogastric tube twice daily for 3 days or 1 week. CS23 significantly reduced ulcer size, and L-NAME significantly delayed healing compared with the vehicle group and significantly inhibited the efficacy of CS23. Although constitutive NOS (cNOS) activity significantly decreased and inducible NOS (iNOS) activity significantly increased in the vehicle group, CS23 significantly inhibited these changes. cNOS immunoreactivity on the vessels and neurons disappeared in the vehicle group, and newly formed vessels as well as neurons were observed with positive endothelial and neuronal NOS immunoreactivity in the CS23-treated group. External administration of bFGF accelerated ulcer healing, with recovery of NO synthesis in both endothelial cells and neurons. These observations suggested that increased NO synthesis with angiogenesis and reinnervation has a beneficial effect on gastric ulcer healing.
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PMID:Basic fibroblast growth factor increases constitutive nitric oxide synthase during healing of rat gastric ulcers. 947 38

1. The influence of hyperammonemia (produced by the continuous intraperitoneal infusion of ammonium acetate for 6 days) on stress-induced gastric ulcer formation was investigated in conscious rats. 2. Continuous ammonium acetate infusion significantly reduced stress-induced gastric ulceration concomitant with an increase in gastric blood flow, as determined using radioactive microspheres. The serum levels of L-arginine as well as nitrite and nitrate (oxidative byproducts of nitric oxide) were increased by ammonium acetate infusion. 3. Prior administration of N omega-nitro-L-arginine methyl ester, a competitive nitric oxide synthase inhibitor, substantially attenuated the increase in gastric blood flow caused by ammonium acetate infusion and diminished the protective effect on gastric ulceration. 4. These findings suggest that the synthesis of endogenous nitric oxide from L-arginine is accelerated by continuous ammonium acetate infusion when the urea cycle remains intact and has a substantial cytoprotective effect on the stomach, probably through maintaining the gastric mucosal microcirculation.
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PMID:Hyperammonemia reduces water immersion--restraint stress gastric ulcers in rats. 959 85

We have recently reported that steady-state gastric mucosal blood flow (GMBF) is decreased in streptozotocin (STZ) diabetic rats, and that their GMBF response to burn-stress is impaired, probably via a nitric oxide (NO)-mediated mechanism. Accordingly, this study was designed to investigate the relation of aldose reductase (AR) and NO synthase to the regulation of GMBF during chronic hyperglycemia. STZ rats were treated with or without chronic oral administration of an AR inhibitor, epalrestat (EPA) and/or an NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). GMBF was measured by laser-Doppler velocimetry (LDV). In the STZ rats, GMBF after a 24-h fasting period was decreased significantly 4 weeks after the onset of diabetes and this was accompanied by an increase in the gastric ulcer index (UI) (a measure of the length of gastric erosions and ulcers). Chronic oral administration of EPA to the STZ rats dose-dependently inhibited the increased UI and the decreased GMBF after the fasting stress, whereas chronic oral administration of L-NAME further increased the UI and further decreased the GMBF. EPA administered in combination with L-NAME to the STZ rats reduced the effects of L-NAME, but the effects did not reach significance. These results suggest that EPA protects the gastric mucosa of diabetic rats, by preventing the decrease in GMBF that is, at least in part, caused by NO-related mechanisms.
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PMID:Epalrestat prevents the decrease in gastric mucosal blood flow and protects the gastric mucosa in streptozotocin diabetic rats. 1021 35

Lafutidine is a new type antiulcer agent with antisecretory and gastroprotective activities. We investigated the effect of lafutidine on indomethacin-induced antral ulcer in refed rats. Subcutaneous indomethacin injection resulted in the formation of gastric antral ulcer. Lafutidine (1-10 mg/kg, p.o.) reduced the area of ulcer in a dose-dependent manner when administered immediately after the indomethacin injection. Capsaicin at 3 mg/kg, p.o. and 16,16-dimethyl prostaglandin E2 at 3 microg/kg, p.o. also reduced the ulcer area. Chemical deafferentation of capsaicin-sensitive neurons or N(G)-nitro-L-arginine treatment aggravated the ulcer formation and abolished the preventive effect of lafutidine and capsaicin. After the induction of gastric ulcer, lafutidine given twice daily for 2.5 days reduced the area of ulcer in a dose-dependent manner with a significant effect at 10 mg/kg, p.o., as compared with that of the control group. In chemically-deafferentated rats, lafutidine did not show any healing effect. Cimetidine (30 mg/kg, p.o.) and famotidine (1 mg/kg, p.o.) had no significant effect on indomethacin-induced antral ulcer. These results may suggest that lafutidine, unlike cimetidine and famotidine, can prevent the indomethacin-induced antral ulcer formation and accelerate the healing of the ulcer in refed rats through mechanisms involving the capsaicin-sensitive afferent neurons and nitric oxide.
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PMID:Antiulcer effect of lafutidine on indomethacin-induced gastric antral ulcers in refed rats. 1046 68

Nitric oxide has been shown to be beneficial for gastric ulcer healing. We determined the relative effects of endothelial and inducible nitric oxide synthases on gastric ulcer healing in rats. Ulcers were induced by serosal application of acetic acid. Ulcer severity, angiogenesis, and nitric oxide synthase expression were assessed 3-10 days later. The effects of inhibitors of nitric oxide synthase were also examined. Inducible nitric oxide synthase mRNA was only detected in ulcerated tissue (maximal at day 3), whereas the endothelial isoform mRNA was detected in normal tissue and increased during ulcer healing. Inducible nitric oxide synthase was expressed in inflammatory cells in the ulcer bed, whereas endothelial nitric oxide synthase was found in the vascular endothelium and in some mucosal cells in both normal and ulcerated tissues. Angiogenesis changed in parallel with endothelial nitric oxide synthase expression. N(6)-(iminoethyl)-L-lysine did not affect angiogenesis or ulcer healing, while N(G)-nitro-L-arginine methyl ester significantly reduced both. In conclusion, endothelial nitric oxide synthase, but not the inducible isoform, plays a significant role in gastric ulcer healing.
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PMID:Endothelial nitric oxide synthase modulates gastric ulcer healing in rats. 1091 43

The aim of this study was to investigate the effect of nitric oxide (NO) on the gastric injury induced by hemorrhagic shock. Hemorrhagic shock was created by withdrawing 3 ml blood/200 g body weight of the rats. Before the hemorrhage, N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v. bolus), D-NAME (10 mg/kg i.v. bolus), or L-arginine (100 mg/kg i.v. bolus and 10 mg/kg/min infusion) + L-NAME were administered. At the end of the 1-hour hypovolemic shock period, histological analysis, gastric ulcer index, gastric myeloperoxidase (MPO) activity, and gastric protein oxidation (PO) levels were determined. In histological analysis a destructive effect of L-NAME (NO synthase inhibitor) was demonstrated. L-NAME treatment increased gastric MPO activity, L-arginine reversed this effect and D-NAME had no effect. Tissue PO activity was found to be increased in L-NAME-treated rats; L-arginine treatment reversed this activity. It is concluded that gastric barrier function is altered after hemorrhagic shock, and L-arginine (NO precursor) can prevent mucosal injury in the stomach. This effect of NO may be on gastric blood flow and can be mediated by tissue neutrophils.
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PMID:Role of nitric oxide in gastric injury induced by hemorrhagic shock in rats. 1094 Jul 85

Gastric ulceration was induced in rats by i.p. injection of the non-steroidal anti-inflammatory drug (NSAID), indomethacin (IND) (30 mg kg(-1)). Pyloric ligation was carried out in each animal before injection to enable collection of the gastric juice. Three hours later, the animals were killed and their stomachs were removed. In the gastric juice, the amounts of mucin, pepsin and HCl were assessed. Gastric mucosa were scrapped for the determination of nitric oxide (NO) (as nitrite) after evaluation of the gastric ulcer index. The influence of arginine (ARG) (300 mg kg(-1)), a NO precursor, N(G)-nitro- l -arginine methyl ester (l -NAME) (50 mg kg(-1)), a non-selective constitutive nitric oxide synthase/inducible nitric oxide synthase (cNOS/iNOS) inhibitor, and the selective iNOS inhibitor aminoguanidine (AMG) (50 mg kg(-1)) were studied. Each NO modulator was injected i.p. 30 min before IND administration. Results indicated that IND elevated gastric acidity by 80% of the normal group, decreased non-significantly mucosal nitrite by 22% and exhibited a remarkably high ulcer index (chi = 17). Neither mucin nor pepsin levels were significantly altered. In comparison with the IND group, pretreatment with l -NAME caused a significant decrease in gastric HCl, further decrease in mucosal nitrite (50% of normal) and a two-fold increase in the ulcer index score (chi = 34), despite the decrease in HCl. AMG did not alter gastric acidity, decreased mucosal nitrite by 38% of the normal value and failed to alter significantly the ulcer index of IND. On the other hand, pretreatment with ARG did not alter the gastric acidity and raised mucosal nitrite by 10% above normal. Surprisingly, ARG improved the gastric ulcer score (chi = 1) almost similar to the normal score (chi = zero). Therefore, this study creates a new pathway for the potential treatment of NSAID gastric ulceration through modulation of NO synthesis, regardless of the effect on gastric acidity.
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PMID:Protective role of nitric oxide in indomethacin-induced gastric ulceration by a mechanism independent of gastric acid secretion. 1139 38

In a rat model of the ischemia-reperfusion with pylorus ligation, gastric ulcer was formed, although gastric acid secretion was reduced. When the polymorphonuclear leukocytes were inactivated in advance, gastric ulcer was not formed, but acid secretion was increased, indicating that gastric acid is not a cause of the ulcer formation in this model. The mechanism of gastric acid suppression accompanied by ischemia-reperfusion was examined in relation to the role of oxygen-free radicals in this rat model. Prior administration of superoxide dismutase did not modulate acid secretion, but N-nitro-L-arginine methyl ester (L-NAME) increased acid secretion. The action of L-NAME was antagonized specifically by L-arginine, but not by D-arginine. S-nitroso-N-acetylpenicillamine did not inhibit basal acid secretion but antagonized the action of L-NAME. Aminoguanidine increased significantly the gastric acid output that was suppressed by ischemia-reperfusion. When polymorphonuclear leukocytes were inactivated by treatment with their antibody, the gastric acid output recovered to the level in the pylorus-ligated rat without ischemia-reperfusion. These results suggested that nitric oxide (NO) produced by the infiltrated polymorphonuclear leukocytes plays an important role in the suppression of acid secretion induced by ischemia-reperfusion.
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PMID:The role of nitric oxide in the gastric acid secretion induced by ischemia-reperfusion in the pylorus-ligated rat. 1147 Feb 62


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