title: Repeated inhalation of bradykinin attenuates adenosine 5'-monophosphate (AMP) induced bronchoconstriction in asthmatic airways.
abstract: Repeated bronchial challenges with inhaled bradykinin lead to a rapid loss of the bronchoconstrictor response and this has been suggested to be due to depletion of contractile neuropeptides from sensory nerve endings. If adenosine 5'-monophosphate (AMP), another potent bronchoprovocant in asthma, and bradykinin share a common pathway in inducing bronchoconstriction in asthmatic subjects, then repeated bradykinin bronchoprovocation tests should reduce the response to subsequent inhalation of AMP. We examined this hypothesis in eight asthmatic subjects in a double-blind, randomized study. On the histamine study day, two consecutive concentration-response studies with inhaled histamine were followed by a third consecutive challenge with AMP and the provocation concentration producing a 20% fall in forced expiratory volume in one second from the post-diluent baseline value (PC20 FEV1) for this agonist was calculated. On the bradykinin study day, two consecutive bronchoprovocation tests with bradykinin were followed by a third inhalation challenge to obtain the PC20AMP value. On a further occasion, the asthmatic subjects underwent two consecutive concentration-response studies with inhaled bradykinin followed by a third consecutive challenge with histamine. On the histamine study day, the geometric mean PC20AMP value was 28.1 mg.ml-1, whilst on the bradykinin study day, the fifteenfold reduction in bradykinin responsiveness after the second bradykinin challenge was accompanied by a significant reduction of the airway responsiveness to AMP, the PC20AMP being 59.8 mg.ml-1. A similar reduction in bradykinin responsiveness failed to alter the airway response to a subsequent inhalation with histamine.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Southhampton General Hospital, UK.
authors.forename: R
authors.initials: R
authors.lastname: Polosa
authors.forename: K
authors.initials: K
authors.lastname: Rajakulasingam
authors.forename: M K
authors.initials: MK
authors.lastname: Church
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
mesh_terms: D000249:Adenosine Monophosphate; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000503:physiopathology; D001920:Bradykinin; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006632:Histamine; D006801:Humans; D008297:Male
chemical_list: D000249:Adenosine Monophosphate; D006632:Histamine; D001920:Bradykinin