N-omega-nitro-L-arginine methyl ester increases airway responsiveness to serotonin but not to acetylcholine in cats in vivo

Background: We previously reported that N^ω-nitro-L-arginine methyl ester (L-NAME) enhances airway responsiveness to inhaled serotonin in cats treated with atropine and propranolol. Objective: To further elucidate the role of nitric oxide (NO) in airway responsiveness, we investigated whether L-NAME induces airway hyperresponsiveness to serotonin and acetylcholine (ACh) in animals with intact innervation. Methods: Cats were anesthetized with pentobarbital sodium (50 mg/kg, i.p.), and mechanically ventilated. To assess airway responsiveness, we measured increase in total pulmonary resistance (R_L) produced by delivering serotonin or ACh aerosol to the airway, and determined PC₂₀₀ (the concentration which caused a 200% increase in R_L). Results: The following results were obtained: (1) Airway responsiveness to serotonin was significantly enhanced by the administration of L-NAME (100 mg/kg) in animals treated with atropine and propranolol. (2) Airway responsiveness to serotonin was also significantly enhanced by L-NAME in animals with intact innervation. (3) In contrast, airway responsiveness to ACh was not changed by the addition of L-NAME in cats with intact innervation. Conclusion: These results suggest that NO modulates non-specific airway responsiveness in animals with intact innervation, presumably by a reflex mechanism.