Objective: To observe the effect of inhaled ipratropium bromide on airway and lung tissue muscarinic receptors (MR) in a rat model of chronic obstructive pulmonary disease (COPD).
Methods: The rat model of COPD was established by chronic exposure with high concentrations of SO(2) gas, COPD rats inhaled aerosolized 0.025% ipratropium bromide solution 10 ml (twice/d, 20min/time). The MR was determined by radioligand binding studies with (3)H-QNB as the ligand.
Results: Compared with that of control, there was a marked increase in MR density on day 30 of treatment with ipratropium but not on day 5. The MR density decreased and close to normal level on the 6th day after cessation of regular therapy with inhaled ipratropium for 30 days. No significant difference was observed in antagonist affinity (Kd) among different time groups of ipratropium therapy.
Conclusions: Chronic exposure to the anticholinergic agent ipratropium bromide produces an up-regulation of airway MR. The airway MR density can recover to normal when treatment stopped. Up-regulation of airway MR is associated with transient bronchoconstriction following cessation of regular ipratropium therapy and lung function deteriorated following long-term inhaled ipratropium bromide.