Effect of vagotomy on airway hyperreactivity to endogenously released neurotransmitters at 18–24 h after inhaled antigen

Abstract

Airway reactivity was examined in anaesthetized guinea-pigs 18–24 h after inhalation challenge of ovalbumin-sensitized animals with ovalbumin. Bronchoconstrictor responses were measured from the increases in pulmonary inflation pressure. The study was undertaken to examine whether ovalbumin challenge induced airway hyperreactivity to neurotransmitters released endogenously by vagal nerve stimulation. Stimulation parameters were selected to cause release of either acetylcholine (0.3 ms pulse width for 3 s, 20 V, 2–40 Hz), both acetylcholine and neuropeptide (5 ms pulse width for 15 s, 20 V, 0.5–8 Hz) or neuropeptide only, using 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 neuropeptide-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–response curves were displaced to the left after ovalbumin challenge compared with saline challenged animals, indicating airway hyperreactivity. This airway hyperreactivity was significant after atropine and suggests an increase in sensitivity to endogenously released neuropeptides rather than acetylcholine. It also indicates that the airway hyperreactivity 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. Comparisons of exogenously administered 5-hydroxytryptamine (5-HT, 300 ng/100 g i.v.) and a single vagal stimulation of 0.3 ms pulse width (cholinergic) revealed no airway hyperreactivity to either stimulus after ovalbumin challenge. However if the vagi were cut, airway hyperreactivity was observed, again suggesting that removal of afferent pathways is important for revealing airway hyperreactivity in the anaesthetized guinea-pig. Ovalbumin challenge caused significant increases in the bronchoconstrictor responses to a single dose of capsaicin (50 μg/100 g i.v.) or dose–response curves to bradykinin. Since these agents release neuropeptides from sensory C-fibres, this is further support for a raised sensitivity to endogenously released neuropeptides.