Bradykinin B2 antagonist HOE 140 inhibits late allergic microvascular leakage in guinea pig airways.
Because bradykinin has potent inflammatory actions, this molecule may be involved in the late allergic response (LAR). We investigated the role of the molecule in airway microvascular hyperpermeability during the LAR. Three weeks after ovalbumin (OVA) sensitization, animals were pretreated with bradykinin B2 receptor antagonist HOE 140 or vehicle for 30 min before the OVA inhalation challenge. The occurrence of LAR was judged by a two-fold increase in transpulmonary pressure (Ptp) from the baseline values. The microvascular permeability in the trachea was assessed by an index defined as the ratio of the area of vasculature labeled by the Monastral blue dye (area density percent). Significant microvascular hyperpermeability were observed during the LAR. The bradykinin concentrations in the bronchoalveolar lavage-fluid (BAL-f) were increased during the LAR. HOE 140 (0.1-10 mg/kg, s.c.) inhibited the airway microvascular hyperpermeability during the LAR dose-dependently. These findings suggest that bradykinin may play an important role in microvascular hyperpermeability during the LAR.
Mashito
Y
Y
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ichinose
M
M
Shirato
K
K
D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability / Q000187:drug effects*; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D043782:Receptor, Bradykinin B2; D014132:Trachea / Q000098:blood supply*
D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; C065679:icatibant; D010047:Ovalbumin; D001920:Bradykinin