EFFECTS OF AIRWAY PARASYMPATHETIC TONE ON RESPONSES TO INTRAVENOUS BRONCHOCONSTRICTOR AGONISTS IN RATS

To test the hypothesis that parasympathetic airway tone may affect air way responsiveness, we measured bronchoconstrictor responses to intrav enous bethanechol (BCh) in anesthetized vagotomized rats with and with out background vagal nerve stimulation and developed a predictive mode l based on pharmacological additivity between endogenous and intraveno us agonists. A high degree of agreement (r(2) = 0.93) between the meas ured and predicted responses indicated that intravenous BCh and parasy mpathetic tone had bronchoconstrictor effects that were pharmacologica lly additive. An expansion of the additive model was used to determine that the percentage of decrease in respiratory system conductance (Gr s) would be a measure of airway response independent of background par asympathetic tone. As predicted, the percentage of decrease in Grs aft er intravenous BCh was minimally affected by background vagal stimulat ion. However, the percentage of decrease in Grs was augmented by vagal stimulation for intravenous 5-hydroxytryptamine hydrochloride, a know n parasympathetic neuromodulator, and for methacholine, an agonist wit h nicotinic as well as muscarinic activity (P < 0.02 for each agonist) . We conclude that airway parasympathetic tone can be a source of vari ability for airway responsiveness when substances having neuromodulato ry activity are involved in the provocative challenge.