Prevention of water immersion stress‐induced gastric lesions through the enhancement of nitric oxide synthase activity in rats

Abstract

Background: Gastric mucosal microcirculation is an important factor in the protection of gastric mucosa, and nitric oxide (NO) plays a crucial role in the regulation of regional blood flow. This study was designed to evaluate the effect of cetraxate, an antiulcer drug, on water immersion stress-induced gastric lesions in relation to the changes in NO synthase activity. Methods: Gastric lesions were induced in rats by water immersion stress. The effects of cetraxate on NO synthase activity with or without stress was determined enzymatically. Changes in gastric mucosal prostaglandin (PG) contents with or without stress were also determined using high-performance liquid chromatography. Gastric mucosal blood flow was measured by hydrogen gas clearance technique. Results : Water immersion stress-induced gastric lesions. Cetraxate significantly mitigated the lesions but N"-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthase, exacerbated the lesions. The favourable effect of cetraxate was remarkably diminished by administration of L-NMMA. NO synthase activity decreased significantly by 6 h after stress. Cetraxate treatment increased NO synthase activity throughout the experiment in rats with or without stress treatment. Water immersion stress decreased all PGs detected, i.e. 6-keto-PGF1,, PGF,,, PGE, and PGD,. Cetraxate prevented stress-induced decreases in PG contents. L-NMMA showed no significant effect on PG contents. Cetraxate increased gastric mucosal blood flow significantly and L-NMMA cancelled out cetraxateinduced increase in blood flow. Conclusions : The pharmacological efficacy of anti-ulcer drugs such as cetraxate might be attributable to the enhancement of NO synthase activity resulting in an increase in gastric mucosal blood flow.Apart from the significant contribution of Helicobucter pylori, gastric acid secretion and cytoprotective factors play an important role in the genesis of gastric ulcers. The local release of vasodilator mediators in the gastric mucosal microcirculation are of paramount importance in the maintenance of mucosal integrity and defence. Prostaglandin (PG), particularly PGI, in humans, PGI, and PGD, in rats, are important vasodilator mediators and adverse effects on gastric mucosa caused by non-Corrrspondcncc to Dr H. Coto,

Influence of Helicobacter pylori infection and cetraxate on gastric mucosal blood flow during healing of endoscopic mucosal resection‐induced ulcers

“…Cetraxate, an anti‐ulcer drug with mucosal protective effects, is reported to increase MBF by enhancing nitric oxide synthase activity 17 . Tachi et al demonstrated that cetraxate increased NO synthase activity in rats with and without stress treatment, and prevented stress‐induced decreases of several PGs in gastric mucosa 18 . In addition, a recently published study has demonstrated that the addition of cetraxate to proton pump inhibitor (PPI)‐based triple H. pylori eradication treatment augmented the eradication rate, especially in smokers, probably by increasing gastric MBF 28 .…”

“…Cetraxate is a widely used anti‐ulcer drug with protective effects on the mucosa. The anti‐ulcer activity of this drug is ascribed to the increase in MBF caused by enhancing nitric oxide synthase activity 17,18 . This study was designed to investigate the effect of H. pylori infection on MBF during human gastric ulcer healing, and the effect of cetraxate on H. pylori ‐induced changes in MBF.…”

Nitric oxide: Relation to integrity, injury, and healing of the gastric mucosa

“…This suggests that such an effect is not a result of any direct vasodilatory action but is the consequence of preventing an action of this NSAID, which, in turn, leads to a reduction of gastric perfusion. Although the mechanisms responsible for these effects may vary Reduction in gastric blood flow after NOS inhibition is associated with: 1Stress induced gastric damage (Qiu et al, 1996) 1Ethanol induced gastric damage (Masuda et al, 1995;Qiu et al, 1996) 2Gastric mucosa epithelial growth (Dembinski et al, 1995) 2Ulcer healing (Takeuchi et al, 1997) NO mediates gastroprotection and mucosal hyperemia induced by: Antiulcer drugs Aluminum antacids (Konturek et al, 1992) Cetraxate (Tachi et al, 1996) Lansoprazol (Murakami et al, 1996) Sucralfate ) Hormones Cholecystokinin Leptin (Brzozowski et al, 1999b) Pentagastrin …”

Efficacy of Triple Therapy Plus Cetraxate for the Helicobacter pylori Eradication in Partial Gastrectomy Patients

“…Its activity is ascribed to promotion of an increase in gastric mucosal blood flow (29). Tachi et al showed that cetraxate might enhance nitric oxide synthase activity and prevent a decrease in the mucosal prostaglandin content, resulting in an increase in gastric mucosal blood flow (30). The addition of cetraxate also has been reported to improve the eradication rate of H. pylori (31).…”