An airway hyperresponsiveness model in rat allergic asthma.
We attempted to obtain a new airway hyperresponsiveness model using DNP-Ascaris extract (DNP-Asc)-induced rat allergic asthma. Male Wistar rats were actively sensitized with DNP-Asc, and challenged in a non-anesthetized state by inhalation of the antigen for 10 min in a chamber. One, 6 and 24 hr after DNP-Asc challenge, the responsiveness of the airway smooth muscles to inhaled acetylcholine (ACh) was determined using a modified Konzett-Rössler method under anesthesia. Twenty four hr after the challenge, a significant and marked airway hyperresponsiveness was seen. The increase in airway responsiveness was significantly inhibited by pretreatments with a leukotriene antagonist, ONO-1078, and a thromboxane synthetase inhibitor, ozagrel, and tended to be inhibited by a PAF antagonist, CV-3988. The hyperresponsiveness induced by DNP-Asc challenge was accompanied by airway inflammation determined by dye exudation. From the above results, it is indicated that a model of airway hyperresponsiveness was established in rats with allergic asthma, and that the chemical mediators involved in the response might be leukotrienes, thromboxane A2 and PAF.
Misawa
M
M
Department of Pharmacology, School of Pharmacy, Hoshi University.
Sugiyama
Y
Y
D000109:Acetylcholine / Q000276:immunology; D000818:Animals; D001200:Ascaris; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity; D002199:Capillary Permeability; D002867:Chromones / Q000494:pharmacology; D003864:Depression, Chemical; D004140:Dinitrophenols; D004195:Disease Models, Animal; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013189:SRS-A / Q000037:antagonists & inhibitors; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014020:Tissue Extracts / Q000276:immunology
D002867:Chromones; D004140:Dinitrophenols; D008689:Methacrylates; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D013189:SRS-A; D014020:Tissue Extracts; C037913:CV 3988; D013930:Thromboxane-A Synthase; C034364:ozagrel; D000109:Acetylcholine; C047681:pranlukast