Premium
Inhibition of neutral endopeptidase potentiates bronchoconstriction induced by neurokinin A in asthmatic patients
Author(s) -
CRIMI N.,
PALERMO F.,
OLIVERI R.,
POLOSA R.,
MAORÌ S.,
MISTRETTA A.
Publication year - 1994
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.1994.tb00206.x
Subject(s) - phosphoramidon , bronchoconstriction , neurokinin a , neprilysin , thiorphan , medicine , histamine , inhalation , asthma , bronchodilation , endocrinology , anesthesia , substance p , bronchodilator , chemistry , neuropeptide , biochemistry , receptor , endothelin receptor , enzyme
Summary The endogenous tachykinins exhibit a range of properties which may he relevant in the pathophysiology of asthma. Their effects on the airways seem to be modulated by a variety of lung peptidases, including neutral endopeptidase (NEP). In order to evaluate the potential role of endogenous NEP activity in modulating tachykinins‐induced bronchconstriction in man in vivo , six atopic asthmatic patients, with a mean FEV 1 value of 3.38 ± 0.76 1, and a histamine PD20 mean value of 0.024 mg. were studied. The influence of inhaled phosphoramidon (a potent NEP inhibitor) was examined against the NKA‐induced bronchospasm in a double‐blind, placebo‐controlled randomized study. Changes in airway calibre were followed as FEV 1 and agonists responsiveness expressed as PD20 and PD15 for histamine and NKA respectively. Patients received nebulized phospharamidon sodium salt (10 −5 M) or a control solution 10 min prior to the bronchoprovocation test with NKA. No significant difference was noticed between any of the study days and after inhaled phosphoramidon on baseline FEV 1 values (3.29 ± 0.90 1) in comparison with the control solution (3.31 ± 0.79 1). Inhaled NKA produced a dose‐dependent fall in FEV 1 values in all the subjects studied with a mean PD15 value of 20.91 × 10 −9 mol. Phosphoramidon administered by inhalation elicited a significant ( P < 0.0l vs baseline and control solution) potentiation in the airway responsiveness to inhaled NKA, the NKA PD15 value decreasing to 9.45 × 10 −9 mol. The present study confirms that inhaled NKA induces a dose‐related bronchconstriction in asthmatic patients and demonstrates that inhaled phosphoramidon potentiates NKA‐induced bronchoconstriction.