Adaptation of Esophageal Mucosa to Acid- and Pepsin-Induced Damage (Role of Nitric Oxide and Epidermal Growth Factor)

To study whether the esophageal mucosa was ableto elicit mucosal adaptation, we induced esophagealdamage by perfusing acidified pepsin in rabbits. Mucosaladaptation was induced by preexposing the esophageal mucosa to a mild irritant (acidified saline)for 60 min prior to acidified pepsin (strong irritant).Macroscopic and microscopic esophageal injury, cellproliferation, and mucosal barrier function(H⁺, K⁺, hemoglobin flux rates)were studied. Preexposure of the esophageal mucosa toacidified saline significantly decreased both themucosal damage and the mucosal barrier dysfunctioninduced by acidified pepsin. The development of this phenomenon wasnondependent on cell proliferation. Concomitanttreatment with either the nitric oxide synthaseinhibitor, N^G-nitro-L-arginine, or theperfusion of immunospecific EGF-receptor antibodies or tyrphostin-25, aninhibitor of the tyrosine kinase activities ligated tothe intracytoplasmatic domain of the EGF receptor,during the preexposure period completely reversed the protection induced by acid. We conclude thatthe rabbit esophageal mucosa shows mucosal adaptation toacid and pepsin. The development of this phenomenon isfast, not dependent on cell proliferation, and dependent, at least in part, on nitric oxideand EGF-receptor-mediated mechanisms.