Airway hyperreactivity follows anaphylactic microshock in anaesthetized guinea-pigs.
Actively sensitized guinea-pigs were challenged with a dose of ovalbumin aerosol (300 micrograms 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 less than 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 micrograms ml-1, 5 s) did not induce airway hyperreactivity, pretreatment with the histamine H1 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.
Daffonchio
L
L
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Payne
A N
AN
Lees
I W
IW
Whittle
B J
BJ
D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000707:Anaphylaxis / Q000503:physiopathology*; D000758:Anesthesia; D000818:Animals; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008297:Male; D011738:Pyrilamine / Q000494:pharmacology; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors
D012701:Serotonin; D011738:Pyrilamine; D000109:Acetylcholine