Luminal hypertonicity and the susceptibility of rabbit esophagus to acid injury

The esophagus is regularly exposed to hypertonic luminal environments, some of which have the capacity to increase epithelial permeability. The present experiments were designed to determine what impact such environments have on epithelial resistance to injury by acid. Rabbit esophageal epithelium mounted in Ussing chambers was exposed to luminal acid while monitoring electrical resistance (R), a marker of epithelial permeability, and morphology was assessed in tissues luminally pretreated with either urea (1 M), mannitol (1 M), or normal Ringer. Hypertonic mannitol, which had little effect on R, was associated with a minor increase in susceptibility to acid injury, pH 1.6. In contrast, hypertonic urea lowered R and was associated with marked injury upon exposure to acid. This susceptibility to acid injury occurred within 15 minutes of exposure and converted a non-damaging concentration of acid (pH 2.0) to a damaging one. Moreover, urea's effects were abolished if it was removed from the bath allowing R to return to baseline before acidification. We conclude that hypertonic luminal environments that impair epithelial barrier function predispose the esophagus to acid injury. Such findings may provide insight into additional mechanisms contributing to the development of heartburn following meals.