title: Vascular permeability and airway narrowing during late asthmatic response in dogs treated with Metopirone.
abstract: Recently, we have developed an animal model of late asthmatic response (LAR) by treating naturally sensitized dogs to Ascaris suum antigen with the cortisol-synthesizing inhibitor, Metopirone. By using this animal model, we examined the contribution of edema in the airway wall to the development of LAR. To study whether airway microvascular leakage is increased in association with LAR, we performed antigen challenge in dogs treated with Metopirone. We measured the amount of extravasated Evans blue (EB) dye from the esophagus, trachea, and large and small bronchi 8 hours after the antigen challenge in dogs demonstrating immediate asthmatic response alone (IAR) and in dogs demonstrating both IAR and LAR. Airway responses to A. suum antigen were assessed by changes in respiratory resistance measured with the force oscillation technique at 3 Hz. EB dye extravasation did not increase significantly from that of control in any tissues in IAR (P greater than 0.10), but in LAR, it increased significantly from that of control (p less than 0.01) and IAR (p less than 0.05) in large and small bronchi. Histologic assessment of vascular permeability revealed that Monastral blue-labeled leaking vessels were only in sections from LAR, and leaking vessels were limited to small vessels (10 to 25 microns) in the trachea, large (diameter, greater than 5 mm) and small bronchi (2 to 4 mm in diameter), and bronchiole. The permeability index defined as the ratio of area of small vessels labeled with Monastral blue to that of the total small vessels in the walls was highest in the small bronchi. LAR significantly increased submucosal thickness of the small bronchi (p less than 0.05) compared with that in IAR. Both EB dye extravasation and permeability index in large and small bronchi also significantly increased during IAR within 3 minutes after the antigen challenge (p less than 0.05), but IAR did not alter the submucosal thickness of the small bronchi. These results imply that the increase in vascular permeability and submucosal thickness, especially in small bronchi, may be an important factor in the pathogenesis of LAR.
authors.affiliation: First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohrui
authors.forename: K
authors.initials: K
authors.lastname: Sekizawa
authors.forename: T
authors.initials: T
authors.lastname: Aikawa
authors.forename: K
authors.initials: K
authors.lastname: Yamauchi
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Takishima
mesh_terms: D000402:Airway Obstruction / Q000139:chemically induced*; D000403:Airway Resistance; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology; D002199:Capillary Permeability; D004285:Dogs; D005070:Evans Blue; D008797:Metyrapone; D015588:Observer Variation; D015203:Reproducibility of Results; D012137:Respiratory System / Q000098:blood supply
chemical_list: D000941:Antigens; D005070:Evans Blue; D008797:Metyrapone