An endothelin receptor antagonist, SB-217242, inhibits airway hyperresponsiveness in allergic mice
| Autor: | Angela C. D'Aprile, Roy G. Goldie, Tracy S. Mann, Glenn J. Self, Peter J. Henry |
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| Rok vydání: | 2002 |
| Předmět: |
Endothelin Receptor Antagonists
Male Pulmonary and Respiratory Medicine Physiology Carboxylic Acids Cell Count Inflammation Pharmacology Allergic inflammation Leukocyte Count Mice Physiology (medical) Edema Macrophages Alveolar Hypersensitivity Leukocytes medicine Animals Endothelin-1 Endothelin receptor antagonist business.industry Antagonist Cell Biology respiratory system respiratory tract diseases medicine.anatomical_structure Indans Immunology Mice Inbred CBA Bronchial Hyperreactivity medicine.symptom Endothelin receptor Airway business Bronchoalveolar Lavage Fluid Respiratory tract |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 283:L1072-L1078 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | Within the airways, endothelin-1 (ET-1) can exert a range of prominent effects, including airway smooth muscle contraction, bronchial obstruction, airway wall edema, and airway remodeling. ET-1 also possesses proinflammatory properties and contributes to the late-phase response in allergic airways. However, there is no direct evidence for the contribution of endogenous ET-1 to airway hyperresponsiveness in allergic airways. Allergic inflammation induced in mice by sensitization and challenge with the house dust mite allergen Der P1 was associated with elevated levels of ET-1 within the lung, increased numbers of eosinophils within bronchoalveolar lavage fluid and tissue sections, and development of airway hyperresponsiveness to methacholine ( P < 0.05, n = 6 mice per group). Treatment of allergic mice with an endothelin receptor antagonist, SB-217242 (30 mg · kg−1· day−1), during allergen challenge markedly inhibited airway eosinophilia (bronchoalveolar lavage fluid and tissue) and development of airway hyperresponsiveness. These findings provide direct evidence for a mediator role for ET-1 in development of airway hyperresponsiveness and airway eosinophilia in Der P1-sensitized mice after antigen challenge. |
| Databáze: | OpenAIRE |
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