Airway hyperreactivity follows anaphylactic microshock in anaesthetized guinea-pigs

Abstract

Actively sensitized guinea-pigs were challenged with a dose of ovalbumin aerosol (300 ωg ml −1, 5 s) that caused submaximal bronchoconstriction (anaphylactic microshock). Airway reactivity to i.v. 5-hydroxytryptamine (5-HT), i.v. acetylcholine (ACh) and aerosolised 5-HT was assessed subsequently. In addition, histological studies were carried out to investigate possible pulmonary recruitment of inflammatory cells following anaphylactic microshock. Following antigen challenge, there was a significant P 0.05 increase in airway reactivity. This phenomenon was temporally separated (60–120 min) from the initial anaphylactic bronchoconstriction, but occurred in the absence of detectable lung pathology other than minor epithelial necrosis. Whilst histamine aerosol (100 ωg ml −1, 5 s) did not induce airway hyperreactivity, pretreatment with the histamine H 1 receptor antagonist mepyramine (2 mg kg −1 i.v.) prevented that occurring following antigen challenge. These observations suggest that in the pathogenesis of airway hyperreactivity, mediator release from resident leukocytes is initially more important than pulmonary infiltration of circulating cells. Depletion of a putative epithelium-derived relaxant factor may also play a contributory role. The anaphylactic release of histamine may modulate the release of secondary mediators of airway hyperreactivity.