Abstract
Corticosteroids are widely used in treatment of COPD. However there is no consensus about their effectiveness at different stages of COPD.
Aim: To evaluate the effect of prednisone (P) on smooth muscle (SM) contraction of bronchi isolated from rats with different stages of COPD.
Methods: Model of COPD was induced in Wistar rats by long-time nitrogen dioxide (NO2) exposure (15 ppm, 1,5 h/day, 60-90 days). Model adequacy was confirmed morphologically and immunohistochemicaly. The bronchial SM contractility was evaluated at different stages of COPD (15, 30, 60, 90 days NO2 exposure). Bronchi (2-6 generations) with intramural ganglions were isolated and placed in perfusion solution. P (10 μg/ml) was added in perfusion solution. SM contractions were determined at electric stimulations preganglionic nerves or SM using the electromechanical displacement sensor.
Results: After 15-day exposure NO2 (acute stage) P decreased the amplitude of bronchial SM contraction caused by stimulation of preganglionic nerves to 29,4±2,5% of the initial level (p<0,01), after 30-day exposure – to 14,7±3,8% (p<0,05), at 60- and 90-day exposure effect of P was absent. With SM stimulation the application of P didn't affect on SM contraction for any duration NO2 exposure. After 90 days in response to SM stimulation prednisone instead of reducing the SM contraction caused its increase up to 111,0±4,9% (p<0,05).
Conclusion: Bronchodilatory effect of P is mediated by neurogenic mechanism. The greatest effect of P manifests in the initial stages of formation of COPD. As the progression of COPD the dilator effect of P is reduced until disappearance (corticosteroid resistance).
- © 2011 ERS