Intratracheal sensitization/challenge-induced biphasic asthmatic response and airway hyperresponsiveness in guinea pigs.
In most experimental model of asthma using guinea pigs, the animals are made to inhale an aerosolized antigen which passes through the nasal cavity. In the present study, we attempted to create an animal model of asthma showing a biphasic asthmatic response and airway hyperresponsiveness, in which the allergic responses are restricted to the lung. Guinea pigs were sensitized by the intratracheal instillation of ovalbumin (OVA)+Al(OH)₃ once a day for 7 d, and then intratracheally challenged with OVA 12 d after the last sensitization. The change in specific airway resistance (sRaw) and airway responsiveness to histamine were measured. Pranlukast (100 mg/kg), theophylline (50 mg/kg), and dexamethasone (10 mg/kg) were orally administered 18 and 2 h before the antigen challenge. The challenge caused a marked biphasic elevation of sRaw with peaks at 5 min and 4 h. At 24 h, airway hyperresponsiveness to histamine was observed. Pranlukast, theophylline, and dexamethasone suppressed the late asthmatic response and airway hyperresponsiveness. The early asthmatic response was inhibited by theophylline and dexamethasone. In conclusion, the intratracheal sensitization and challenge caused a biphasic asthmatic response and airway hyperresponsiveness in guinea pigs. This model may be useful for the evaluation of anti-asthma drugs.
Department of Pharmacology, Kobe Pharmaceutical University, Japan. mizutani@kobepharma-u.ac.jp
Nobuaki
N
Mizutani
Shouichi
S
Inui
Shin
S
Yoshino
Takeshi
T
Nabe
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000941:Antigens / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage*; D013806:Theophylline / Q000494:pharmacology / Q000627:therapeutic use; D014132:Trachea
D018927:Anti-Asthmatic Agents; D000941:Antigens; D002867:Chromones; D003907:Dexamethasone; D006632:Histamine; D010047:Ovalbumin; D013806:Theophylline; C047681:pranlukast