Oxygen Radicals Produce Airway Constriction and Hyperresponsiveness in Anesthetized Cats

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Abstract
Using 30 anesthetized cats, we examined whether oxygen radicals produce airway constriction or hyperresponsiveness. In one group, we administered aerosolized xanthine (0.1%) for 3 min followed by aerosolized xanthine oxidase (XO) (1 U/ml) for 5 min in order to generate oxygen radicals enzymatically in the airways. Pulmonary resistance (Rl) instantaneously increased from 14.8 ± 0.9 to 30.8 ± 1.4 cm H2O/L/s (p < 0.01). The increase in Rl was significantly depressed by prior administration of polyethylene glycol-superoxide dismutase (PEG-SOD) or polyethylene glycolcatalase (PEG-CAT). In a second group, in order to examine changes in airway responsiveness, we studied acetylcholine (ACh) challenge before and 30, 60, and 120 min after inhalations of xanthine and XO. After xanthine-XO, the airways were hyperresponsive to ACh at 30 and at 60 min (p < 0.05) but not at 120 min. The geometric means of ACh provocative concentrations that caused an increase in Rl of 10 cm H2O/L/s above the baseline value before and 30, 60, and 120 min after xanthine-XO were 0.25, 0.045, 0.073, and 0.15%, respectively. The increase in responsiveness to ACh was significantly correlated with the increase in Rl after xanthine-XO inhalation (r = 0.88, p < 0.05). These data support the concept that oxygen radicals generated by xanthine-XO inhalation may induce bronchoconstriction and airway hyperresponsiveness.