Hypertonic saline increases tight junction permeability in airway epithelium

Asthmatics are known to react to inhaled hyperosmolar solution. Therefore, the effect of hyperosmolar salt solutions on tight junctions of the airway epithelium was investigated by electron microscopy. Rat trachea was perfused with different concentrations of sodium chloride (NaCl) and then fixed from the luminal side with glutaraldehyde to which the electron dense tracer lanthanum chloride had been added. Lanthanum penetrated 3 +/- 1% of the tight junctions in trachea perfused with 295 mOsm Krebs-Ringer's buffer (KRB). Adding NaCl to the KRB (KRB-NaCl) increased osmolarity of the solution. After perfusion with 589 or 876 mOsm KRB-NaCl, lanthanum was observed in the lateral intercellular spaces in 50 +/- 11 and 57 +/- 6%, respectively. The effect of hyperosmolarity was reversible and only 6 +/- 1% of the tight junctions were penetrated after perfusion with 295 mOsm KRB solution following 589 mOsm KRB-NaCl perfusion. Adding mannitol to the KRB to an osmolarity of 589 mOsm only caused 5 +/- 1% of the tight junctions to open, even though osmotic effects were observed. Opening the tight junctions with hyperosmolar salt solutions may play a role in exercise-induced asthma. It may also open the prospect for increased penetration of inhaled drugs into the interstitium and the circulation.