Contribution of bradykinin B-1 and B-2 receptors in allergen-induced bronchial hyperresponsiveness

Bradykinin (BK) is a peptide mediator generated at sites of inflammation an d its effects are mediated through constitutively expressed B-2 receptor or through induction of B-1 receptors. We examined the role of these receptor s in bronchial hyperresponsiveness (BHR). Brown-Norway rats sensitized with ovalbumin (OA) and AI(OH), intraperitoneally, were exposed 3 wk later to e ither saline or OA aerosol. B-1 receptor antagonist desArg(10)[Hoe140] (200 nmol/kg or 1 mu mol/kg, intraperitoneally) or B-2 receptor antagonist Hoe1 40 (200 nmol/kg, intraperitoneally) was administered 30 min before allergen exposure. Hoel40 had no effect on OA-induced BHR to acetylcholine (ACh) an d bronchoalveolar lavage fluid (BALF) cellular profiles, but inhibited bron choconstriction to BK (p < 0.04). At both doses, desArg(10)[Hoe140] dose-de pendently inhibited allergen-induced BHR to ACh (p < 0.01), but had no effe ct on bronchoconstriction to BK or baseline ACh responsiveness. The inflamm atory cells in BALF were not affected apart from reduced lymphocyte numbers at the highest dose. B-1 receptor mRNA expression measured by Northern ana lysis was increased after allergen exposure in sensitized lungs, with a pea k at 2 to 6 h after exposure, whereas B-2 receptor mRNA expression remained unchanged. Newly induced BK B-1 receptors may be involved in allergen-indu ced BHR to ACh, whereas constitutive B-2 receptors mediate BK-induced bronc hoconstriction.