R. Sorkness et al., EFFECTS OF AIRWAY PARASYMPATHETIC TONE ON RESPONSES TO INTRAVENOUS BRONCHOCONSTRICTOR AGONISTS IN RATS, Journal of applied physiology, 77(6), 1994, pp. 2698-2702
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.