Airway Responsiveness to Intravenous and Inhaled Acetylcholine in the Guinea Pig after Cigarette Smoke Exposure

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Abstract
Exposure of conscious guinea pigs to cigarette smoke results in bronchial hyperresponsiveness. To examine the mechanisms involved, we measured airway responses to increasing doses of intravenous or inhaled acetylcholine in guinea pigs exposed to cigarette smoke (n = 20) or to air (n = 20). After exposure the guinea pigs were anesthetized, paralyzed, and studied in a pressure-sensitive body plethysmograph while ventilated through a tracheostomy. Two and 6 puffs of an aerosol of increasing concentrations (0.05 to 500 µig/ml) of acetylcholine were delivered via the tracheostomy. Intravenous acetylcholine was delivered in boluses of 0.1 ml of increasing concentrations (0.5 to 50,000 µg/ml) via a catheter in an external jugular vein. Pulmonary resistance (Rl), dynamic compliance (Cdyn), and heart rate (HR) were measured at baseline (after aerosolized or intravenous saline) and after each dose of acetylcholine. The peak responses to both inhaled and intravenous acetylcholine were rapid in onset (less than 15 s), short-lived (3 to 4 breaths), and were noncumulative. The baseline Rl, Cdyn, and HR were not different in the smoke and air exposure groups. In the intravenous acetylcholine group, there were no differences in Rl, Cdyn, and HR responses between the air and smoke exposure groups. In the inhaled acetylcholine group, the dose-response curve was shifted to the left (p < 0.05) and reached a higher maximal response (p < 0.01) after smoke exposure. Inhaled acetylcholine also produced a greater fall in HR (p < 0.05) in the smoke-exposed group. These data suggest that cigarette smoke exposure induces bronchial hyperresponsiveness in the guinea pig by increasing the permeability of the airway wall to inhaled acetylcholine.