Neutral endopeptidase inhibitor potentiates endothelin-1-induced airway smooth muscle contraction.
J Appl Physiol (1985)
; 73(3): 1108-13, 1992 Sep.
Article
em En
| MEDLINE
| ID: mdl-1400023
ABSTRACT
To study the role of neutral endopeptidase (NEP) on endothelin-1-induced contraction of the airway smooth muscle, we examined the contractile effect of endothelin-1 in the isolated guinea pig trachea and human bronchus in the presence or absence of NEP inhibitor phosphoramidon. After incubation with phosphoramidon (10(-8) to 10(-5) M), we added endothelin-1 cumulatively from 10(-11) to 10(-7) M to the airway tissues in organ baths. Phosphoramidon significantly potentiated the endothelin-1-induced contraction in a concentration-dependent fashion in both guinea pig trachea and human bronchus, and it shifted the concentration-response curves to the left. Because NEP is known to cleave tachykinins, we next studied whether endothelin-1 contracts airway tissues by releasing endogenous tachykinins from bronchial C-fibers. After incubation with phosphoramidon (10(-5) M), we added endothelin-1 cumulatively from 10(-11) to 10(-7) M to the tissues that were treated with capsaicin to deplete the tachykinins. Phosphoramidon significantly potentiated the endothelin-1-induced contraction in the capsaicin-treated tissues, suggesting that endothelin-1 causes the contraction, at least in part, without releasing tachykinins. In contrast to the effect of phosphoramidon, captopril (an angiotensin-converting enzyme inhibitor), leupeptin (a serine protease inhibitor), and bestatin (an aminopeptidase inhibitor) did not modulate the effect of endothelin-1-induced contraction in both guinea pig trachea and human bronchus. From these results, we conclude that NEP plays an important role in regulating endothelin-1-induced contraction in the guinea pig trachea and human bronchus.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Músculos Respiratórios
/
Neprilisina
/
Endotelinas
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article
País de afiliação:
Japão