Effects of mast cell stabilizers on a new bronchial asthma model using compound 48/80 in dogs.
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 compound 48/80 infusion into the bronchial artery produces an asthma-like bronchoconstriction, the main chemical mediator involved in this response would be histamine acting through H1-receptors, and effects of mast cell stabilizers can be evaluated with this model.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002744:Chlorpheniramine / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D014628:Vagotomy; D062367:ortho-Aminobenzoates / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine
D003509:Cyclohexanecarboxylic Acids; D006634:Histamine H1 Antagonists; D062367:ortho-Aminobenzoates; D002744:Chlorpheniramine; D003189:p-Methoxy-N-methylphenethylamine; C038303:NCO 650; D006632:Histamine; C012293:tranilast; D004205:Cromolyn Sodium