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 anti-ulcer 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(G)-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-PGF1alpha, PGF2alpha, PGE2 and PGD2. 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 cetraxate-induced 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.