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Chronic airway hyperreactivity is a hallmark feature of asthma, but animal models of airway hyperreactivity often utilize a single antigen challenge. Therefore, we compared the airway hyperreactivity produced by single and multiple antigen challenges in ovalbumin-sensitized guinea pigs. Significant (2-fold) leftward shifts in dose-response curves for i.v. methacholine- or LTD4-induced bronchoconstriction in anesthetized and ventilated animals occurred 24 h following a single ovalbumin challenge. This nonspecific airway hyperreactivity was prevented by pretreatment with ketotifen or dexamethasone. However, airway hyperreactivity was no greater 24 h following the last of 3 daily antigen challenges than after 1 challenge and was absent 72 h following one antigen challenge. These results raise concern over the similarity of antigen-induced airway hyperreactivity in guinea pigs to the chronic airway hyperreactivity in asthmatics.

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