Am. J. Respir. Crit. Care Med., Volume 163, Number 6, May 2001, 1320-1325

Function of Pulmonary Neuronal M₂ Muscarinic Receptors in Stable Chronic Obstructive Pulmonary Disease

LING SAI ON, PETCHARA BOONYONGSUNCHAI, SAMANTHA WEBB, LISA DAVIES, PETER M. A. CALVERLEY, and RICHARD W. COSTELLO

Univesity of Liverpool, Liverpool, United Kingdom

Anticholinergic drugs often cause a considerable degree of bronchodilation in patients with chronic obstructive pulmonary disease (COPD). Pulmonary neuronal M₂ muscarinic receptors function to limit the magnitude of vagally induced bronchoconstriction. We hypothesized that the effectiveness of anticholinergic agents in patients with COPD may reflect increased vagal reactivity due to dysfunction of M₂ muscarinic receptors. The function of M₂ receptors and the magnitude of vagally induced bronchoconstriction were assessed in subjects with normal lung function and in subjects with COPD. A nasal cold dry air challenge was used to induce a bronchoconstriction, measured as a change in airway resistance (Raw) at 5 Hz (R5) using impulse oscillometry. In subjects with COPD R5 rose from 0.68 ± 0.06 to 0.74 ± 0.07 kPa/L/s after the cold dry air challenge (p < 0.01) and in the control subjects R5 rose from 0.34 ± 0.03 to 0.39 ± 0.03 kPa/L/s (p < 0.01). The bronchoconstriction was inhibited by pretreatment with ipratropium bromide, indicating that it was vagally mediated. In both groups of subjects pretreatment with the selective M₂ muscarinic receptor agonist pilocarpine (5 mg/ml) prevented the cold air-induced bronchoconstriction, indicating normal function of M₂ receptors. These studies indicate that M₂ muscarinic receptors are functional in subjects with stable COPD.

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