抄録
Development of a nonimmunologically induced experimental asthma model using compound 48/80 was attempted. Male mongrel dogs anesthetized with pentobarbital-Na were immobilized with decamethonium bromide under artificial respiration. Airway resistance was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO). Inhalation of compound 48/80 caused no change in VO even in high concentrations up to a 1 % solution. Infusion of compound 48/80 into the bronchial artery at a dose of 0.2 mg/min for 10 min by using the right bronchial perfusion method caused a marked increase in VO accompanied by decreases in perfusion pressure and systemic blood pressure. The compound 48/80-induced bronchoconstriction was inhibited 58% by surgical vagotomy and was almost abolished by chlorpheniramine (10 mg/kg, intraduodenally (i.d.)). Disodium cromoglycate (inhalation of 1% solution along with 5 mg/kg, i.v.), tranilast (300 mg/kg, i.d.) and NCO-650, a new antiallergic drug (100 mg/kg, i.d.) significantly inhibited the compound 48/80-induced bronchoconstriction. These results indicate that 1) compound 48/80 infusion into the bronchial artery produces an asthma-like bronchoconstriction, 2) the main chemical mediator involved in this response would be histamine acting through H1-receptors, and 3) effects of mast cell stabilizers can be evaluated with this model.
