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.
Department of Pharmacology, School of Pharmacy, Hoshi University.
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Misawa
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Sugiyama
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