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Mechanisms of airway hyperreactivity to bradykinin induced by allergen and endotoxin in the brown Norway rat
Başlık:
Mechanisms of airway hyperreactivity to bradykinin induced by allergen and endotoxin in the brown Norway rat
Yazar:
Ellis, Karen M., author.
ISBN:
9780438085114
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (212 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Özet:
Airway hyperreactivity (AHR) is a critical component of bronchial asthma. The present studies were carried out to investigate the mechanisms of AHR to bradykinin, based on bronchoconstrictor (in vivo) and contractile (parenchymal strip in vitro) responses to bradykinin following ovalbumin (OA) or endotoxin (lipopolysaccharide, LPS) challenge using Brown Norway rats. The receptor(s), cell types and mechanism(s) involved in the augmented response to bradykinin have been evaluated. In naive or actively sensitised, saline-challenged animals bradykinin induced bronchoconstriction. However, intratracheal challenge with OA or LPS induced profound changes in the response of the airways to bradykinin, (and adenosine and methacholine) which were related to the bronchospasmogen used and the time after challenge that the spasmogens were administered. Specifically, OA (0.3 mg kg-1,-24 h) or LPS (0.3 mg kg-1,-1 h) induced a marked and optimal AHR to bradykinin. Augmented contractile responses to bradykinin were also seen in vitro at these time points. Challenge with OA (0.3 mg kg-1) led to time-dependent changes in leukocyte populations and protein and eosinophil peroxidase levels in bronchoalveolar lavage (BAL) fluid. Histological analysis of the lungs of OA-challenged animals demonstrated perivascular and peribronchial lymphocytic and leukocyte infiltration and oedema. Over the time course studied, a poor correlation was seen between the inflammatory response and the augmented bradykinin response. Moreover, budesonide substantially inhibited the inflammation but failed to inhibit the bronchoconstrictor response to bradykinin. One hour after LPS challenge, there was a marked increase in the levels of TNFalpha in the BAL fluid. Furthermore, incubation with TNFalpha in the in vitro studies resulted in significant augmentation of the contractile response to bradykinin. Pharmacological analysis implicated the exclusive involvement of the bradykinin B2 receptor in both OA- and LPS-induced AHR to bradykinin. The response after allergen challenge does not involve mast cells, products of COX or 5-LO metabolism, or tachykinins, which also excludes sensory nerves, but is partly mediated by muscarinic receptor activation. In vitro, the enhanced response to bradykirun involves COX products and there is no cholinergic component. Combined inhibition of angiotensin-converting enzyme and neutral endopeptidase resulted in a striking potentiation of the response, which suggests that downregulation of peptidase activity in the lung after allergen challenge may be an important factor in the augmented response to bradykinin. The response after LPS challenge does not involve mast cells but is partly mediated by muscarinic receptor activation. TNFalpha appears to have an important role in augmenting the response to bradykinin after LPS challenge.
Notlar:
School code: 1543
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(686929.1) | 686929-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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