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The authors investigated the physical role of the airway epithelium in response to changes in the airway surface fluid's composition by superperfusing the lumen with nonisotonic solutions. Morphological studies and measurements of changes in ion content in the underlying connective tissue (CT) were carried out. The study used an experimental model of isolated rat trachea. The trachea was mounted in an extraluminal organ bath with Ringer's solution, whereas the lumen was perfused with a fluid in which the NaCl concentration was varied. The tissue was fixed for electron microscopy or frozen for X-ray microanalysis. X-ray microanalysis showed that the Na and Cl content of the CT increased with increasing luminal NaCl concentrations. This increase was significantly larger when the tight junctions had been damaged by exposure to ethylene glycol tetra-acetic acid. At high luminal NaCl concentrations, electron microscopy showed that a significant influx of fluid into the CT had occurred in tracheae with damaged epithelia. Damage to the epithelium also resulted in ultrastructural changes in myofibroblasts, increased diameter of capillaries, and thickening of the basement membrane. The epithelium evidently plays a crucial role in the regulation of the ion content of the connective tissue in the airway wall, and epithelial damage may explain the greater sensitivity to provocation with hyperosmolar sodium chloride solutions or airway dehydration observed in patients with asthma or cystic fibrosis.

Effect of luminal osmolarity on ion content of connective tissue in rat trachea after epithelial damage