Lack of a role for bradykinin in allergen-induced airway microvascular leakage and bronchoconstriction in the guinea pig.
We have investigated the role of bradykinin in allergen-induced airway microvascular leakage and bronchoconstriction in sensitized guinea pigs. We used a selective bradykinin B2 receptor antagonist, HOE140, which has been shown to prevent the airway effects induced by bradykinin. Lung resistance (RL) was measured for 6 min after challenge with allergen. Extravasation of Evans blue dye into airway tissues was used as an index of the airway microvascular leakage. Aerosolized ovalbumin (5 mg/ml, 30 breaths) induced a significant increase in RL and leakage of dye in the trachea, main bronchi and intrapulmonary airways in the ovalbumin-sensitized guinea pigs. HOE140 given by inhalation (200 microM, 60 breaths) had no effect on the airway microvascular leakage and bronchoconstriction induced by the allergen. I.v. HOE140 (200 nmol/kg) did not significantly inhibit these airway responses. We conclude that bradykinin-mediated mechanism may not play a significant role in airway microvascular leakage or bronchoconstriction induced by allergen.
Sakamoto
T
T
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Barnes
P J
PJ
Chung
K F
KF
D000280:Administration, Inhalation; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D016084:Bronchoconstriction / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D004396:Coloring Agents / Q000378:metabolism; D005070:Evans Blue / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005260:Female; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology
D000319:Adrenergic beta-Antagonists; D000336:Aerosols; D065168:Bradykinin Receptor Antagonists; D004396:Coloring Agents; D005070:Evans Blue; C065679:icatibant; D010047:Ovalbumin; D001920:Bradykinin