Allergen-induced Bronchial Hyperresponsiveness

Bradykinin (BK) is a peptide mediator generated at sites of inflammation and its effects are mediated through constitutively expressed B 2 receptor or through induction of B 1 receptors. We examined the role of these receptors in bronchial hyperresponsiveness (BHR). Brown-Norway rats sensitized with ovalbumin (OA) and Al(OH) 3 intraperitoneally, were exposed 3 wk later to either saline or OA aerosol. B 1 receptor antagonist desArg 10 [Hoe140] (200 nmol/kg or 1 m mol/kg, intraperitoneally) or B 2 receptor antagonist Hoe140 (200 nmol/kg, intraperitoneally) was administered 30 min before allergen exposure. Hoe140 had no effect on OA-induced BHR to acetylcholine (ACh) and bronchoalveolar lavage fluid (BALF) cellular profiles, but inhibited bronchoconstriction to BK (p , 0.04). At both doses, desArg 10 [Hoe140] dose-dependently inhibited allergen-induced BHR to ACh (p , 0.01), but had no effect on bronchoconstriction to BK or baseline ACh responsiveness. The inflammatory cells in BALF were not affected apart from reduced lymphocyte numbers at the highest dose. B 1 receptor mRNA expression measured by Northern analysis was increased after allergen exposure in sensitized lungs, with a peak 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-induced BHR to ACh, whereas constitutive B 2 receptors mediate BK-induced bronchoconstriction. Huang T-J, Haddad E-B, Fox AJ, Salmon M, Jones C, Burgess G, Chung KF. Contribution of bradykinin B 1 and B 2 receptors in allergen-induced bronchial hyperresponsiveness. AM J RESPIR CRIT CARE MED 1999;160:1717–1723.