EFFECT OF VAGOTOMY ON AIRWAY HYPERREACTIVITY TO ENDOGENOUSLY RELEASEDNEUROTRANSMITTERS AT 18-24 H AFTER INHALED ANTIGEN

Airway reactivity was examined in anaesthetized guinea-pigs 18-24 h af ter inhalation challenge of ovalbumin-sensitized animals with ovalbumi n. Bronchoconstrictor responses were measured from the increases in pu lmonary inflation pressure. The study was undertaken to examine whethe r ovalbumin challenge induced airway hyperreactivity to neurotransmitt ers released endogenously by vagal nerve stimulation. Stimulation para meters were selected to cause release of either acetylcholine (0.3 ms pulse width for 3 s, 20 V, 2-40 Hz), both acetylcholine and neuropepti de (5 ms pulse width for 15 s, 20 V, 0.5-8 Hz) or neuropeptide only, u sing the latter parameters in the presence of atropine. The vagi were paired for stimulation and in some experiments were cut central to the stimulation point. Frequency-response curves for acetylcholine- and n europeptide-mediated bronchoconstrictor responses to vagal stimulation when the nerves were intact revealed no airway hyperreactivity after ovalbumin challenge. The presence.of atropine failed to reveal airway hyperreactivity. However, when the vagi were cut, the frequency-respon se curves were displaced to the left after ovalbumin challenge compare d with saline challenged animals, indicating airway hyperreactivity. T his airway hyperreactivity was significant after atropine and suggests an increase in sensitivity to endogenously released neuropeptides rat her than acetylcholine. It also indicates that the airway hyperreactiv ity is dependent on removal of the afferent vagal pathways. Frequency- response curves for cholinergic stimulation (0.3 ms) with intact vagi revealed no airway hyperreactivity after antigen challenge. Comparison s of exogenously administered 5-hydroxytryptamine (5-HT, 300 ng/100 g i.v.) and a single vagal stimulation of 0.3 ms pulse width (cholinergi c) revealed no airway hyperreactivity to either stimulus after ovalbum in challenge. However if the vagi were cut, airway hyperreactivity was observed again suggesting that removal of afferent pathways is import ant for revealing airway hyperreactivity in the anaesthetized guinea-p ig. Ovalbumin challenge caused significant increases in the bronchocon strictor responses to a single dose of capsaicin (50 mu g/100 g i.v.) or dose-response curves to bradykinin. Since these agents release neur opeptides from sensory C-fibres, this is further support for a raised sensitivity to endogenously released neuropeptides. (C) 1998 Elsevier Science B.V. All rights reserved.