Nitric oxide is generated in smooth muscle layer by neurokinin A and counteracts constriction in guinea pig airway

Citation
T. Imasaki et al., Nitric oxide is generated in smooth muscle layer by neurokinin A and counteracts constriction in guinea pig airway, NITRIC OXID, 5(5), 2001, pp. 465-474
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
ISSN journal
1089-8603 → ACNP
Volume
5
Issue
5
Year of publication
2001
Pages
465 - 474
Database
ISI
SICI code
1089-8603(200110)5:5<465:NOIGIS>2.0.ZU;2-J
Abstract
It has been reported that several bronchoconstrictors generate nitric oxide (NO), counteracting bronchoconstriction, and removal of bronchial epitheli a reduces NO production. However, it has not been elucidated whether neurok inin A (NKA), a potent bronchoconstrictor liberated from nerve terminals, g enerates NO. Specific questions in this study were (1) does NKA also genera te NO, (2) does NO counteract NKA-induced bronchoconstriction, and (3) does the NO generation require bronchial epithelial cells? In an in vivo study exogenous as well as endogenous (capsaicin-induced) NKA increased airway op ening pressure (P-ao) and the exhaled NO level, and both were inhibited by an antagonist selective for NK2 receptor (a receptor for NKA), SR48968. The exhaled NO level became negligible with an inhibitor of NO synthase (NOS) type 1-3 (N-G-nitro-L-arginine methyl ester, L-NAME) with increased P-ao, b ut not with a NOS type 2 inhibitor. In an in vitro study, NKA increased the nitrite/nitrate level in superfused fluid of tracheal segments. Removing s mooth muscle reduced nitrite/nitrate in the fluid to negligible levels, whi le the level was unchanged with removal of the epithelia. Pretreatment with L-NAME enhanced the tension of epithelia-removed tracheal segments. These findings indicate that (1) NKA generates NO, (2) NO counteracts NKA-induced bronchoconstiriction, and (3) NKA activates NOS in the muscle layer, indep endently of bronchial epithelia. (C) 2001 Academic Press.