Nitric oxide and superoxide anion in low-grade esophagitis induced by acidand pepsin in rabbits

It has been suggested that free radicals are involved in esophagitis. To st udy the role and potential interaction of superoxide anion and nitric oxide (NO) in low-grade esophagitis, we perfused acidified pepsin (30 min every 12 hr) for seven days in rabbits treated with different agents to modulate the generation of these radicals. Measurements included macroscopic and mic roscopic damage, superoxide anion generation, mucosal nitric oxide synthase activity, and peroxynitrite formation. Low-grade esophagitis was associate d with increased nitric oxide synthase mucosal activity and mucosal damage was dose-dependently increased by treatment with the NO synthase inhibitor N-G-nitro-L-arginine. Superoxide anion was scarcely generated in the mucosa , but this was not accompanied by any change in the activity of mucosal sup eroxide dismutase. Treatment with superoxide dismutase did not improve muco sal damage. Generation of peroxynitrites was not detected. In conclusion, n itric oxide is involved in the mucosal defense of the esophagus against aci d- and pepsin-induced damage. Superoxide anion generation seems irrelevant in the induction of low-grade esophagitis and not sufficient to interact wi th nitric oxide to generate measurable mucosal peroxynitrite radicals.