Pharmacological characterization of the late phase reduction in lung functions and correlations with microvascular leakage and lung edema in allergen-challenged Brown Norway rats

Abstract Late phase airflow obstruction and reduction in forced vital capacity are characteristic features of human asthma. Airway microvascular leakage and lung edema are also present in the inflammatory phase of asthma, but the impact of this vascular response on lung functions has not been precis...

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Bibliographic Details
Published in:Pulmonary pharmacology & therapeutics 2013-12, Vol.26 (6), p.677-684
Main Authors: Mauser, Peter J, House, Aileen, Jones, Howard, Correll, Craig, Boyce, Christopher, Chapman, Richard W
Format: Article
Language:English
Subjects:
Allergens - immunology
Animals
Arachidonic Acid - metabolism
Asthma - physiopathology
Betamethasone - pharmacology
Brown Norway rats
Capillary Permeability - drug effects
Capillary Permeability - physiology
Disease Models, Animal
Forced expiratory maneuvers
Inflammation
Inflammation - immunology
Inflammation - physiopathology
Lipoxygenase - metabolism
Male
Mediators of inflammation
Medical Education
Microvessels - immunology
Microvessels - pathology
Ovalbumin - immunology
Peak Expiratory Flow Rate
Prostaglandin-Endoperoxide Synthases - metabolism
Pulmonary edema
Pulmonary Edema - immunology
Pulmonary Edema - physiopathology
Pulmonary/Respiratory
Rats
Rats, Inbred BN
Vital Capacity
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Summary:Abstract Late phase airflow obstruction and reduction in forced vital capacity are characteristic features of human asthma. Airway microvascular leakage and lung edema are also present in the inflammatory phase of asthma, but the impact of this vascular response on lung functions has not been precisely defined. This study was designed to evaluate the role of increased lung microvascular leakage and edema on the late phase changes in forced vital capacity (FVC) and peak expiratory flow (PEF) in allergen-challenged Brown Norway rats using pharmacological inhibitors of the allergic inflammatory response. Rats were sensitized and challenged with ovalbumin aerosol and forced expiratory lung functions (FVC, PEF) and wet and dry lung weights were measured 48 h after antigen challenge. Ovalbumin challenge reduced FVC (63% reduction) and PEF (33% reduction) and increased wet (65% increase) and dry (51% increase) lung weights. The antigen-induced reduction in FVC and PEF was completely inhibited by oral treatment with betamethasone and partially attenuated by inhibitors of arachidonic acid metabolism including indomethacin (cyclooxygenase inhibitor), 7-TM and MK-7246 (CRTH2 antagonists) and montelukast (CysLT1 receptor antagonist). Antagonists of histamine H1 receptors (mepyramine) and 5-HT receptors (methysergide) had no significant effects indicating that these pre-formed mast cell mediators were not involved. There was a highly significant ( P  
ISSN:1094-5539
1522-9629
DOI:10.1016/j.pupt.2013.03.005