Possible roles of the peripheral vagal nerve in histamine-induced bronchoconstriction in guinea-pigs

Although the importance of the vagal nerve in the pathogenesis of bronchial asthma has been reported, its precise contribution is still not fully understood. To shed more light on this area, we evaluated the possible contribution of vagal reflex in histamine-induced bronchoconstriction (HIB), and decided the site of action of histamine on the vagal nerve. For this purpose, we studied the effects of the bilateral cervical vagotomy, hexamethonium (2 mg.kg-1) or tetrodotoxin (0.5 mg.kg-1) on HIB (8 micrograms.kg-1, iv) in anaesthetized and mechanically-ventilated guinea-pigs. We also studied whether or not atropine (1 mg.kg-1) decreases HIB after vagotomy, including either the treatment of hexamethonium or tetrodotoxin. Airway responses were assessed by measurement of pulmonary resistance. The following results were obtained; 1) the response to histamine was significantly enhanced by the vagotomy, hexamethonium or tetrodotoxin; 2) propranolol increased HIB, and HIB was further enhanced by the vagotomy in the animals treated with propranolol; 3) atropine significantly suppressed HIB after the vagotomy, hexamethonium or tetrodotoxin. These results suggest that the postganglionic vagal nerve plays an excitatory role in HIB through the release of acetylcholine from the nerve terminals. It is also suggested that the vagal reflex mainly exhibits an inhibitory role in the HIB of guinea-pigs, presumably by the action of the nonadrenergic inhibitory nervous system.