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Mechanisms of hyperresponsiveness in the human nasal airway: role of kinins and nitrous oxide

Turner, PJ; (1999) Mechanisms of hyperresponsiveness in the human nasal airway: role of kinins and nitrous oxide. Doctoral thesis , University of London. Green open access

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Abstract

Allergic rhinitis is a condition which affects over 15% of the population in the United Kingdom. The pathological process involves two stages - nasal inflammation, and the development of a nasal hyperresponsiveness to allergen and a range of other non-specific stimuli. There is currently little information on the pathological process underlying hyperresponsiveness. This thesis presents an investigation into the potential role of kinins and nitric oxide in causing nasal hyperresponsiveness in man. In the non-allergic subject, platelet activating factor (PAF) can be used to induce a nasal hyperresponsiveness which is similar to that observed in allergic rhinitis. The data obtained suggests that PAF-induced nasal hyperresponsiveness is mediated by an action of kinins at the bradykinin B2 receptor. Experiments in subjects with seasonal allergic rhinitis also imply a similar role for kinins in allergen-induced hyperresponsiveness. Furthermore, the kinins may be involved in the recruitment of inflammatory cells which is seen in the hyperresponsive state. Data is presented which indicates that kinin generation can potentiate inflammatory cell recruitment, both in vitro and in vivo in the human nasal airway. However, application of exogenous bradykinin alone does not cause a nasal hyperresponsiveness, nor an influx of inflammatory cells. While suggestions are made as to the precise role of kinins, the mechanism does not appear to be dependent on subsequent neuropeptide release. Interestingly, modulating the degree of nitric oxide in the human nasal airway can also induce a hyperresponsiveness. The data therefore imply that activation of the bradykinin B2 receptor is necessary in both PAF- and allergen-induced nasal hyperresponsiveness in man. In addition, the generation of kinins may be important in the recruitment of inflammatory cells in allergic rhinitis.

Type: Thesis (Doctoral)
Title: Mechanisms of hyperresponsiveness in the human nasal airway: role of kinins and nitrous oxide
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third-party content has been removed from this e-thesis.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1514507
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