IPRATROPIUM DECREASES AIRWAY SIZE IN DOGS BY PREFERENTIAL M(2) MUSCARINIC RECEPTOR BLOCKADE IN-VIVO

Background: Two major groups of drugs are available to prevent broncho constriction: beta-agonists and muscarinic blocking agents. Ipratropiu m is the most commonly used anticholinergic agent to treat chronic obs tructive pulmonary disease. The authors studied anti-muscarinic agents to determine if they ate as effective bronchodilators as beta-adrener gic agents and if not to identify the mechanism of their reduced effec tiveness. Methods: Six anesthetized dogs were studied using high-resol ution computed tomography to measure changes in the cross-sectional ar ea of conducting airways induced by cumulative doses of ipratropium wi th and without gallamine, a selective M(2) muscarinic receptor blocker , and after metaproterenol. Results: Metaproterenol dilated the airway s and ipratropium constricted the airways. Ipratropium in concentratio ns of 0.01 and 0.1 mg/ml constricted the airways to 22 +/- 2% and 20 /- 3% of control respectively (P < 0.01), whereas larger concentration s caused bronchodilation After complete blockade of the hi, receptors by pretreatment with intravenous gallamine, the bronchoconstrictor eff ect of ipratropium was abolished, and ipratropium dilated the airways by 16 +/- 8% and 27 +/- 10% of pre-gallamine baseline after doses of 0 .01 and 0.1 mg/ml respectively(P < 0.01). Conclusion: Low-dose ipratro pium can decrease airway size by the initial, preferential blockade of neuronal M(2) muscarinic receptors, whereas a larger dose of ipratrop ium blocks M(2) muscarinic receptors on airway smooth muscle, resultin g in bronchodilation.