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

Abstract

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. 31 barrier-bred pigs were used, of which 24 pigs were actively-sensitised to Ascaris suum. Leukotriene D(4) (LTD(4)) 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 CysLT(1)-receptor antagonist, on LTD(4)- and allergen-induced responses were investigated. LTD(4) (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 LTD(4) (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). LTD(4) causes constriction of the pig bronchi and of the bronchial circulation via activation of the CysLT(1) 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.