Effect of inhaled bradykinin on indices of airway responsiveness in asthmatic subjects.
Asthma is characterized by airway hyperresponsiveness, a physiopathological abnormality which may result from the complex interplay between inflammatory cells and proinflammatory mediators. Although kinins are thought to play a role in the pathogenesis of bronchial asthma, it is not known whether bradykinin is able to induce airway hyperresponsiveness. We have, therefore, investigated the effect of inhaled bradykinin on the changes in airway calibre and in airway hyperresponsiveness to histamine, in a double-blind, randomized study of nine asthmatic subjects. Subjects were studied on two study periods, separated by at least 15 days. On the first day of each study period, subjects inhaled either a single dose of bradykinin or methacholine (placebo) with changes in airway calibre being followed as forced expiratory volume in one second (FEV1) and as the maximum expiratory flow rate measured at 70% of the vital capacity below total lung capacity (TLC) from a partial forced expiratory manoeuvre (Vp30) at 3, 5, 10, 15, 30, 45 and 60 min, and then every hour for 7 h. Airway responsiveness to histamine, expressed as the provocative concentrations producing a 20% fall in FEV1 and 40% fall in Vp30 (PC20FEV1 and PC40Vp30), was measured at 3 and 7 h after inhaling the agonists, then on days 1, 3, 7 and 14. Inhalation of bradykinin caused rapid bronchoconstriction that peaked at 3-5 min. When compared to placebo, no significant difference in histamine responsiveness was seen after bradykinin in terms of changes in PC20FEV1 values.(ABSTRACT TRUNCATED AT 250 WORDS)
Istituto Malattie Apparato Respiratorio, University of Catania, Italy.
R
R
Polosa
K
K
Rajakulasingam
G
G
Prosperini
S
S
Bellofiore
S
S
Britten
L V
LV
Milazzo
S T
ST
Holgate
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D008448:Maximal Expiratory Flow Rate / Q000187:drug effects; D016210:Methacholine Chloride / Q000494:pharmacology; D014109:Total Lung Capacity / Q000187:drug effects; D014797:Vital Capacity / Q000187:drug effects
D016210:Methacholine Chloride; D006632:Histamine; D001920:Bradykinin