Effect of endothelium-derived relaxing factor on the gastric lesion induced by HCl in rats

Effect of HCl on the endothelium-dependent increase in mucosal blood flow and effect of endothelium-derived relaxing factor (EDRF) inhibitors or nitrites on the HCl-induced gastric lesion were studied to clarify the effect of EDRF on the formation of gastric lesion in rats. Topical application of 0.6 N HCl on the gastric mucosa inhibited the endothelium-dependent increase in mucosal hemodynamics estimated using organ-reflectance spectrophotometry induced by vagal stimulation or acetylcholine, but not by papaverine. Collagenase, gossypol, hemoglobin and ascorbic acid have been reported to inhibit the endothelium-dependent vasodilation, inhibited increase in mucosal hemodynamics induced by vagal stimulation and acetylcholine. These inhibitors and methylene blue significantly enhanced the gastric lesion induced by 0.45 N HCl. Intra-arterial or topical application of nitrites (sodium nitrite and isoamyl nitrite) increased mucosal hemodynamics. Oral administration of nitrites prevented the formation of 0.6 N HCl-induced gastric lesion. These results suggest that EDRF plays an important role in the protection of gastric mucosa against HCl. Reduced endothelium-dependent increase in mucosal blood flow may be an etiology of gastric lesion in rats.