1. The mechanism of bradykinin-induced bronchoconstriction in asthma
- Author
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Polosa, Riccardo
- Subjects
615.1 ,Allergy ,Inflammatory response - Abstract
Airway inflammation is a charcteristic finding in asthma. The mechanism linking this inflammatory process to the fundamental abnormalities of bronchial hyperresponsiveness (BHR) and variable airflow limitation in this disese is the release and the continuous formation of biologically active mediators formed de novo in the inflamed airways. Inflammatory mediators such as bradykinin are generally held to contribute to the pathophysiological derangement characteristic of asthma. The present thesis describes a series of investigations aimed at elucidating the mechanism(s) by which bradykinin induces bronchoconstriction and its relevance to bronchial asthma by evaluating its pharmacology and physiology in human studies. The mode of action of bradykinin in provoking bronchoconstriction in asthmatic subjects does not seem to involve the release of functionally active prostanoids and histamine. This response is likely to be mediated via a B2 receptor as the B1 selective agonist [desArg9]-bradykinin has no effect on airway function in asthmatic subjects and as a result of cross-tachyphylactic studies with bradykinin and kallidin. Tachyphylaxis to inhaled bradykinin is specific for the nonapeptide and independent to the production of bronchoprotective prostaglandins. Although bradykinin has a number of pharmacological activities pertinent to the pathogenesis of asthma, we failed to demonstrate its ability in causing BHR. When injected intradermally in man, both bradykinin and kallidin elicit a dose-related increase in wheal and flare which is likely to be mediated via the activation of specific B2 receptors. Pretreatment with topical capsaicin, an irritant which is known to elicit neuropeptides depletion from sensory nerves, greatly attenuates skin responses induced by bradykinin. Investigations on the mechanism of action of bradykinin-induced bronchospasm in asthmatics have the potential of exploring unusual components of the pathophysiology of bronchial asthma. In being an indirect bronchoprovocant with unique features, bradykinin inhalation should prove to be an interesting method of testing 'indirect' non-specific airways hyperresponsiveness in asthma and as such might be helpful in evauating the efficacy novel anti-asthma drugs.
- Published
- 1993