Mediator involvement in antigen-induced bronchospasm and microvascular leakage in the airways of ovalbumin sensitized Brown Norway rats

1 To determine which mediators are involved in antigen-induced bronchospasm and microvascular leakage in the airways of ovalbumin sensitised Brown Nor way rats we investigated the effect of a histamine H-1 receptor antagonist, mepyramine, a 5-HT receptor antagonist, methysergide, and a cysleukotriene -1 receptor antagonist, montelukast. 2 Ovalbumin at 1 mg kg(-1) i.v. caused a significant increase in microvascu lar leakage in the airways and at 3 mg kg(-1) i.v. caused a significant inc rease in airways resistance. 3 Histamine (1 mg kg(-1) i.v.), 5-HT (0.1 mg kg(-1) i.v.) and leukotriene D -4 (LTD4, 50 mug kg(-1) i.v.) caused a significant increase in microvascula r leakage in the airways. 4 Mepyramine (1 mg kg(-1) i.v.), methysergide (0.1 mg kg(-1) i.v.), or mont elukast (30 mg kg(-1) i.v.) inhibited histamine, 5-HT or LTD4-induced micro vascular leakage respectively. 5 Methysergide (0.1 mg kg(-1) i.v.) reduced ovalbumin-induced microvascular leakage in the trachea and at 0.3 mg kg(-1) i.v. inhibited bronchospasm (3 8 and 58%, respectively). Montelukast (30 mg kg(-1) p.o.) reduced ovalbumin -induced microvascular leakage in airway tissue to basal levels (78%) and i nhibited ovalbumin-induced bronchospasm (50%). Mepyramine (3 mg kg(-1) i.v. ) had no effect on ovalbumin-induced leakage or bronchospasm. 6 A combination of all three compounds (mepyramine, methysergide and montel ukast) reduced ovalbumin-induced microvascular leakage in airway tissue to basal levels (70-78%) and almost completely inhibited bronchospasm (92%). 7 Antigen-induced bronchospasm appears to equally involve the activation of 5-HT and cysleukotriene-1 receptors whereas ovalbumin-induced microvascula r leakage appears to be predominantly mediated by cys-leukotriene-1 recepto rs.