Regulation of baseline cholinergic tone in guinea-pig airway smooth muscle

1. We quantified baseline cholinergic tome in the trachealis of mechanically ventilated guineapigs and determined the influence of vagal afferent nerve activity on this parasympathetic tone. 2. There was a substantial amount of baseline cholinergic tone in the guinea-pig trachea, eliciting contractions of the trachealis that averaged 24.6 +/- 3.5% (mean +/- S.E.M) Of the maximum attainable contraction. This tone was essentially abolished by vagotomy or ganglionic blockade, suggesting that it was dependent upon on-going pre-ganglionic input arising from the central nervous system. 3. Cholinergic tone in the trachealis could be markedly and rapidly altered (either increased or decreased) by changes in ventilation (e.g. cessation of ventilation; hyperpnoea; slow, deep breathing) and by lung distention (via positive end-expiratory pressure). These effects were not accompanied by marked alterations in bloodgases and were abolished by vagotomy or atropine. By contrast, tachykinin receptor antagonists, which abolished capsaicin-induced bronchospasm, were without effect on baseline cholinergic tone. This and other evidence suggests that capsaicin-sensitive nerves have little if any influence on baseline parasympathetic tone. Likewise, while activation of afferent nerves innervating the larynx can alter airway parasympathetic nerve activity, transection of the superior laryngeal nerves was without effect on baseline cholinergic tone. 4. Cutting the vagus nerves caudal to the recurrent laryngeal nerves, thus leaving the preganglionic parasympathetic innervation of the trachealis intact but disrupting all afferent nerves innervating the lungs and intrapulmonary airways, abolished baseline cholinergic tone in the trachea. Sham vagotomy or cutting the vagi caudal to the lungs did not reduce baseline cholinergic tone. 5. The results indicate that baseline airway cholinergic nerve activity is necessarily dependent upon afferent nerve activity arising from the intrapulmonary airways and lungs. More specifically, the data are consistent with the hypothesis that on-going activity arising from the nerve terminals of intrapulmonary rapidly adapting receptors determines the level of baseline airway cholinergic tone.