Effect of neutral endopeptidase inhibitor on airway function and bronchial responsiveness in asthmatic subjects.
We determined the effect of an inhibitor of neutral endopeptidase, acetorphan, on the skin responses to substance P and on the bronchostrictor effects of sodium metabisulphite aerosol in asthmatic subjects. One hour following ingestion of acetorphan (200 mg) or placebo tablets, cutaneous responses to substance P were performed in four subjects. In seven subjects, bronchial challenge with increasing concentrations of sodium metabisulphite solutions was performed and the concentration required to cause a 20% fall in baseline FEV1 determined (PC20). On the acetorphan day, there was a significant increase in the wheal and flare responses to substance P and to the diluent (0.9% NaCl) alone. However, there was no significant effect of acetorphan on the PC20 metabisulphite. We conclude that metabisulphite airway challenge in vivo may not invoke the release of endogenous neuropeptides. However, the degree of inhibition of neuropeptide breakdown by the oral dose of acetorphan used may not have been optimal.
Nichol
G M
GM
Department of Thoracic Medicine, National Heart and Lung Institute and Royal Brompton Hospital, London, UK.
O'Connor
B J
BJ
Lecomte
J M
JM
Chung
K F
KF
Barnes
P J
PJ
D000328:Adult; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D012867:Skin / Q000276:immunology; D013373:Substance P / Q000008:administration & dosage / Q000276:immunology; D013447:Sulfites / Q000037:antagonists & inhibitors; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000494:pharmacology
D013447:Sulfites; D013373:Substance P; C049331:racecadotril; C030981:metabisulfite; D015244:Thiorphan; D015260:Neprilysin