title: Bradykinin causes airway hyperresponsiveness and enhances maximal airway narrowing. Role of microvascular leakage and airway edema.
abstract: The relationship between bronchial edema and airway responsiveness was studied in cats in situ. Five cats were exsanguinated, and the bronchial arteries were perfused. We monitored pulmonary resistance (RL), and the provocative dose of acetylcholine (ACh) required to produce a 300% increase in RL (PD300) was determined. Bronchial vascular permeability was measured by quantifying extravasation of Evans blue (EB) dye. Bradykinin (BK) and ACh were administered via the bronchial arteries to increase leakage and bronchoconstriction, respectively. BK preperfusion (for 30 min) significantly increased bronchial vascular permeability to four times the control values (p < 0.05). BK preperfusion did not alter baseline RL but caused hyperresponsiveness to ACh, with log [PD300 (mole)] of -6.53 +/- 0.42 (mean +/- SD) and -6.90 +/- 0.30, before and after BK, respectively (p < 0.01). Furthermore, the maximal airway narrowing after BK was 58% higher than before BK (p < 0.01). Histologic study showed peribronchial edema after BK. The enhancement of maximal airway narrowing was significantly correlated with the degree of EB dye extravasation. These results suggest that BK causes airway hyperresponsiveness to ACh and increases maximal airway narrowing, possibly because of airway edema.
authors.affiliation: First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Ichinose
authors.forename: M
authors.initials: M
authors.lastname: Miura
authors.forename: U
authors.initials: U
authors.lastname: Katsumata
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Takishima
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001920:Bradykinin / Q000009:adverse effects*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000175:diagnosis / Q000473:pathology; D001985:Bronchial Provocation Tests; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema; D005069:Evaluation Studies as Topic; D015203:Reproducibility of Results
chemical_list: D000109:Acetylcholine; D001920:Bradykinin