Abstract
Introduction: During exacerbations of obstructive lung diseases, inflammation and the accompanying bronchoconstriction lead to significant airway narrowing, i.e. resistive breathing (RB). In order to distinguish between the effects of the mechanical stressor and the underlying inflammation we developed a RB model via tracheal banding (TB), and investigated the effects of RB in mice with pre-existing lung inflammationinduced by endotoxin inhalation. Since smooth muscle tone is a crucial determinant of bronchoconstriction and involves nitric oxide (NO) signaling through soluble guanylyl cyclase (sGC) activation, the expression of sGC was studied. Materials and Methods: Adult C57BL/6 mice underwent resistive breathing for 24 hours by placing a nylon band around the extrathoracic trachea, providing a 50% tracheal occlusion. The following groups were studied: 1. TB mice and quietly breathing sham operated mice (controls) 2. Mice treated with inhaled lipopolysaccharide (LPS) pseudomonas aeruginosa 10mg/3ml via nebulization and controls. 3. Mice treated with LPS 24 hours prior TB. Mice were sacrificed 24h post operation. Results: Mice subjected to resistive breathing via TB, exhibited a more pronounced increase in bronchoalveolar lavage fluid cellularity and protein content compared with mice treated with LPS alone. By using forced oscillation technique, TB further increased tissue elasticity and airway resistance. The most pronounced decrease in the expression of sGCα1 and β1 subunits was observed in the group subjected to LPS inhalation and TB. Conclusion: TB aggravates pre-existing lung inflammation and sGC downregulation implicating new insights into the mechanisms during obstructive lung disease exacerbations.
- © 2014 ERS