Cysteinyl leukotrienes in porcine acute allergic airway reactions: bronchial and vascular effects

Abstract:

Objective and design: The role of cysteinyl leukotrienes (cysLTs) in the acute allergic airway reaction in the pig was investigated, with focus on the effects on the bronchial circulation, and compared with histamine-induced effects. Material: 31 barrier-bred pigs were used, of which 24 pigs were actively-sensitised to Ascaris suum. Methods: Leukotriene D₄ (LTD₄) and histamine were injected intravenously (i.v.) and given as an aerosol to non-sensitised pigs. Seventeen animals, sensitised to Ascaris suum, were challenged with Ascaris antigen aerosol. The effect of MK-571, a CysLT₁-receptor antagonist, on LTD₄- and allergen-induced responses were investigated. Results: LTD₄ (2 nmol/kg) i.v. injection increased the airways resistance (R_aw) by 46 ± 20% and reduced bronchial vascular conductance (BVC) by 38 ± 2%. Both these effects were blocked by MK-571 (0.1 mg/kg i.v.). Histamine injections (i.v.) in equimolar doses caused similar dose-dependent increases in R_aw, (22 ± 7%) but induced vasodilatation and an increase in BVC (22 ± 8%). Aerosolised LTD₄ (4 nmol/kg) caused a decrease in BVC but did not affect R_aw. In sensitised pigs, challenge with Ascaris aerosol led to an acute increase in Raw (198 ± 57%) and increase in BVC (62 ± 35%). MK-571 (0.5 mg/kg i.v.) pre-treatment did not significantly affect these responses (n = 9). Conclusions: LTD₄ causes constriction of the pig bronchi and of the bronchial circulation via activation of the CysLT₁ receptor and may counteract histamine-induced vasodilatory effects. However, in the allergen-induced acute airway response in the pig, cysLTs do not seem to be important bronchoconstrictive mediators.