We have previously used the normal lower esophageal sphincter (N-LES) of human organ donors to examine the physiologic signal transduction of lower esophageal sphincter (LES) circular muscle. Now, for the first time, we have obtained a human LES specimen with esophagitis (E-LES) and characterized its pathophysiologic mechanical and inflammatory profiles.

E-LES was examined histologically, and its in vitro circular muscle contraction and production of inflammatory mediators were compared with those of N-LES.

E-LES exhibited scattered erosions and displayed inflammatory cells in the epithelial layer, basal zone hyperplasia, and elongation of lamina propria papillae, characteristic of chronic reflux esophagitis. E-LES muscle strips developed lower in vitro tone (0.78 g) than N-LES (3.3 ± 0.2 g). E-LES tone was essentially restored to normal by the H₂O₂ scavenger catalase, suggesting that H₂O₂ was responsible for reduction of tone. NOX5 cDNA was higher and H₂O₂ levels were 4 times higher in E-LES circular muscle (0.85 nmol/mg protein) than in N-LES (0.19 ± 0.05 nmol/mg protein). When N-LES smooth muscle was incubated in H₂O₂ (70 μmol/L, 2 hours), platelet activating factor (PAF), prostaglandin E₂ (PGE₂), and F₂-isoprostane increased 2.5, 5.2, and 36 times, respectively. In E-LES, levels of PAF, PGE₂, and F₂-isoprostane were 4, 6, and 40 times, respectively, higher than in N-LES. PAF, PGE₂, and F₂ isoprostane produced dose-dependent reductions in tone of N-LES muscle strips.

We conclude that an excessive production of H₂O₂ triggers an increased production of PAF, PGE₂, and F₂-isoprostane, which are responsible for reducing LES tone in human esophagitis.