Effects of antiallergic drugs on bronchial and cutaneous anaphylaxis in Lewis rats

Abstract

Effects of antiallergic agents on 2,4-dinitrophenylated Ascaris extract (DNP-As)-induced bronchial asthma were studied in Lewis rats, and compared with those on passive cutaneous anaphylaxis (PCA). Effects of methysergide and chlorpheniramine on the bronchial asthma model were also investigated. Rats were actively sensitized with DNP-As antigen and with killed Bordetella pertussis. After 8 d, asthmatic response was provoked by inhalation of DNP-As. The bronchomotor response was measured with a modified Konzett-Rössler method in diaphragm-sectioned rats. The inhalation of DNP-As caused a marked asthmatic bronchoconstriction without significant effect on systemic blood pressure and heart rate. Disodium cromoglycate (DSCG), 10 mg/kg, i.v., trans-4-guanidinomethylcyclohexanecarboxylic acid p-tert-butylphenyl ester hydrochloride (NCO-650) and tranilast at doses of 30 and 100 mg/kg, intraduodenally, significantly inhibited the asthmatic response. Chlorpheniramine and methysergide at a dose of 1 mg/kg, i.v. also significantly inhibited it. The above doses of NCO-650 and tranilast significantly inhibited 48 h PCA, while DSCG almost abolished the PCA. These results indicate that 1) NCO-650 and tranilast inhibited both the asthmatic response and PCA in almost the same degree, 2) DSCG inhibited PCA much more strongly than asthmatic response, and 3) histamine and 5-hydroxytryptamine may be involved in this asthmatic response.