Effects of luminal hypertonicity on rabbit esophageal epithelium

The human esophagus is exposed daily to luminal contents that are hypertonic with respect to blood. Because the effects of such exposure are unknown, we investigated the impact of luminal hypertonicity on esophageal epithelial structure and (barrier and transport) function. Rabbit esophageal epithelium was mounted in Ussing chambers and exposed luminally to hypertonic (1,200 mosmol/kgH2O) solutions of mannitol, urea, or NaCl or to normal Ringer solution (300 mosmol/kgH2O). The potential difference (PD), short-circuit current (Isc), and resistance (R) were monitored and, after exposure, tissues were assessed morphologically by light and electron microscopy. Hypertonic mannitol had no significant effect on the electrical or morphological properties of the tissue. However, hypertonic urea and NaCl increased Isc by 91 +/- 31% and 305 +/- 51%, respectively, and decreased R by 20 +/- 6% and 57 +/- 3%, respectively (both P < 0.05 vs. Ringer or mannitol). Furthermore, serosal ouabain blocked the urea-induced increase in Isc completely and the NaCl-induced increase partially (65%) but had no effect on the decline in R. The decline in R for both urea and NaCl was associated with increased [14C]mannitol fluxes and, morphologically, with dilated intercellular spaces but not cell necrosis. These data suggest that hypertonic urea and NaCl, but not hypertonic mannitol, stimulate net Na+ transport in esophageal epithelium and increase permeability via the paracellular route. Notably, the effects of hypertonic urea and NaCl occur rapidly at clinically relevant osmolalities and, though reversible, resolve more slowly. We conclude that hypertonic luminal environments can significantly alter esophageal epithelial structure and function, but that the impact of such exposure depends as much on the nature of the solute as on its osmolality and duration of contact.