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

The authors investigated the physical role of the airway epithelium in resp onse to changes in the airway surface fluid's composition by superperfusing the lumen with nonisotonic solutions. Morphological studies and measuremen ts 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 w as mounted in an extraluminal organ bath with Ringer's solution, whereas th e lumen was perfused with a fluid in which the NaCl concentration was varie d. The tissue was fixed for electron microscopy or frozen for X-ray microan alysis. X-ray microanalysis showed that the Na and Cl content of the CT increased w ith increasing luminal NaCl concentrations. This increase was significantly larger when the tight junctions had been damaged by exposure to ethylene g lycol tetra-acetic acid. At high luminal NaCl concentrations, electron micr oscopy showed that a significant influx of fluid into the CT had occurred i n tracheae with damaged epithelia. Damage to the epithelium also resulted i n ultrastructural changes in myofibroblasts, increased diameter of capillar ies, 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 hypersomolar sodium chloride solutions or airway dehydration observed in patients with asthma or cystic fibrosis.