Nonadrenergic inhibitory nervous system in human airways.

Human airways, from the middle of the trachea to the distal bronchi, were studied in vitro for the presence of inhibitory nerves. The tissue was obtained from operations and from recent autopsies. Electrical field stimulation of the tissues demonstrated cholinergic, excitatory nerves and their effect was blocked by atropine. Field stimulation of the tissues, in the presence of atropine, relaxed the smooth muscle even when the muscle was contracted by histamine. The field stimulation-induced relaxation was neither blocked nor modified by adrenergic blocking agents. Maximum relaxation of the bronchial muscle was obtained with a pulse duration of 1-2 ms, 70 V, and frequencies of 20 Hz and greater. The tracheal smooth muscle showed 85% of maximal relaxation with a frequency of 10 Hz. Tetrodotoxin, blocked the field stimulation-induced relaxation for pulse durations of 2 ms; this indicated that nerves were being stimulated. The airway system shows some of the characteristics of the nonadrenergic inhibitory system in the gastrointestinal tract and of the system reported in the guinea pig trachealis muscle. No evidence of adrenergic inhibitory fibers was found in the bronchial muscle with either pharmacological or histochemical techniques. These findings suggest that the nonadrenergic inhibitory system is the principal inhibitory system for the smooth muscle of human airways. We suggest that a defect in the airway system, such as that shown in the gastrointestinal tract, may be an explanation for the hyperreactive airways of asthma and chronic bronchitis.