Prostaglandins mediate bradykinin-induced reduction of exhaled nitric oxide in asthma.
Bradykinin (BK) is a mediator of inflammation in asthma with potent bronchoconstrictor actions. Endogenous release of nitric oxide may inhibit BK-induced bronchoconstriction. This study investigated whether bradykinin inhalation could modulate exhaled NO levels in normal and asthmatic subjects, and whether the bradykinin-induced effects were mediated through the production of cyclo-oxygenase products in patients with asthma, by studying the effect of the cyclo-oxygenase inhibitor, L-acetylsalicylic acid (L-ASA). Exhaled NO concentration and forced expiratory volume in one second (FEV1) were measured by chemiluminescence following inhalation of increasing concentrations of BK. In asthmatics (n=11), BK induced a dose-dependent decrease in exhaled NO concentration from 21.3+/-1.6 to 6.+/-0.5 parts per billion (ppb) (p<0.01) at the highest concentration, associated with a significant fall in FEV1. In normal subjects (n=10), the exhaled NO concentration fell from 7.2+/-0.13 to 4.3+/-0.51 ppb (p<0.001) 15 min, after a single inhalation of BK, but without a significant change in FEV1. In asthmatic subjects, pretreatment with inhaled L-ASA (90 x mg x mL(-1), 4 mL) did not alter exhaled NO levels, but prevented a BK-induced fall in exhaled NO concentration, as indicated by a significant increase in exhaled NO levels at the provocative concentration of BK causing a 20% fall in FEV1, (5.7 +/- 0.94 ppb after placebo and 12.0 +/- 1.8 ppb after L-ASA; p<0.05). L-ASA significantly reduced bronchial responsiveness to BK 3.9-fold (p<0.01). Inhaled bradykinin induced bronchoconstriction and a reduction in exhaled nitric oxide levels in asthmatic subjects, an effect that is partly mediated by cyclo-oxygenase products.
Kharitonov
S A
SA
Dept of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK.
Sapienza
M M
MM
Chung
K F
KF
Barnes
P J
PJ
D000280:Administration, Inhalation; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D001249:Asthma / Q000378:metabolism*; D001920:Bradykinin / Q000008:administration & dosage* / Q000494:pharmacology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D016022:Case-Control Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D001241:Aspirin; D001920:Bradykinin