Physiological and pharmacological characterization of an in vitro vagus nerve-trachea preparation from guinea-pig.

The trachea with the vagus nerves attached was isolated from guinea-pigs. Contractile responses to nerve stimulation or to drugs were measured as pressure changes in the fluid-filled lumen. Electrical stimulation of the vagus nerves caused a prompt increase in the intratracheal pressure with an optimum frequency of stimulation between 20 and 30 Hz. The response to the left vagus was somewhat stronger than the response to the right vagus. Carbachol caused a maximum pressure increase which was about twice that achieved by bilateral stimulation of the vagus nerves at 20 Hz. In the presence of physostigmine the two sources of stimuli were equally effective. The excitatory response to stimulation of the vagus nerves was completely inhibited by hexamethonium, atropine and terbutaline. This indicates that the excitatory response is mediated via ganglia with end-organ responses mediated exclusively by muscarinic receptors and functionally antagonized by stimulation of beta 2-adrenoreceptors. The trachea preparation exhibited an intrinsic tone which was reduced by terbutaline and indomethacin but not by atropine or hexamethonium. It is probable that prostaglandins are involved in the generation of intrinsic tone. Noradrenaline caused a concentration dependent inhibition of the vagally mediated contractions of the trachea which was antagonized by propranolol and yohimbine. When tracheal tone was induced by carbachol only propranolol was effective thus indicating both pre- and postsynaptic effects of noradrenaline. The present study has shown that the isolated vagus nerve-trachea is a stable and useful preparation for the evaluation of drugs acting at various levels of the contractile responses of the trachea.