Dissociation between bronchial hyperreactivity in vivo and reduced beta-adrenoceptor sensitivity in vitro in allergen-challenged guinea pigs.
In a recently developed guinea pig model of allergic asthma, we investigated the relationships between allergen-induced bronchial hyperreactivity in vivo, tracheal smooth muscle function in vitro, and the number of inflammatory cells in the bronchoalveolar lavage. At 6 h after allergen provocation (after the early asthmatic reaction) bronchial hyperreactivity to histamine aerosol was observed, which was still present, but reduced, at 24 h after the challenge (after the late asthmatic reaction). The severity of bronchial hyperreactivity at 6 h and at 24 h after each of four daily allergen provocations was progressively reduced. The contractile properties of tracheal smooth muscle preparations in response to methacholine or histamine were not changed at 6 h and 24 h after a single allergen provocation, as well as at 24 h after the fourth of the repeated provocations. However, the sensitivity to isoprenaline-induced relaxation of a half-maximal contraction obtained with methacholine or histamine was significantly reduced at 24 h after either a single or the fourth of the repeated provocations. The time course of the reduced beta-adrenoceptor sensitivity in vitro did not correlate with that of bronchial hyperreactivity in vivo. However, it was parallelled by a progressive infiltration of inflammatory cells in the airways, suggesting that mediators from these cells may decrease airway smooth muscle beta-adrenoceptor sensitivity.
Santing
R E
RE
Department of Pharmacology and Therapeutics, University Centre for Pharmacy, Groningen, Netherlands.
Schraa
E O
EO
Vos
B G
BG
Gores
R J
RJ
Olymulder
C G
CG
Meurs
H
H
Zaagsma
J
J
D000485:Allergens; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D000485:Allergens; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol