Neurally mediated nonadrenergic relaxation in cat airways occurs independent of cholinergic mechanisms.

Activation of the nonadrenergic noncholinergic (NANC) inhibitory system in cat airways causes coincident release of acetylcholine from vagal nerve terminals. The present study was undertaken to determine if neurally released acetylcholine is involved in initiating or modulating activity in the lung NANC inhibitory system. Electrical field stimulation experiments were performed on isolated segments of cat trachea and bronchi and additional studies were conducted in intact anesthetized, mechanically ventilated cats. In isolated airways, frequency-dependent NANC relaxations of bethanechol contracted tissues were identical to NANC responses of airways contracted with 5-hydroxytryptamine. This result suggested that muscarinic receptor activation did not influence NANC inhibitory system function. In additional studies where agents that inhibited or potentiated the actions of acetylcholine were used, similar results were obtained. Pretreatment of tissues with hexamethonium or atropine did not alter NANC frequency response curves. Contractile responses evoked by field stimulation were potentiated by neostigmine and abolished by hemicholinium treatment; NANC relaxation responses were not significantly affected by either agent. In intact cats, neostigmine pretreatment did not alter the magnitude or duration of vagally mediated NANC bronchodilation. Acetylcholine administered as an aerosol to cats treated with atropine did not mimic the NANC response. These findings suggest that NANC inhibitory system function in cat airways is neither dependent upon nor modulated by neurally released acetylcholine.