In:
Journal of Applied Physiology, American Physiological Society, Vol. 83, No. 1 ( 1997-07-01), p. 46-51
Abstract:
Nagase, Takahide, Tomoko Aoki, Teruaki Oka, Yoshinosuke Fukuchi, and Yasuyoshi Ouchi. ET-1-induced bronchoconstriction is mediated via ET B receptor in mice. J. Appl. Physiol. 83(1): 46–51, 1997.—Endothelin (ET)-1 is one of the most potent agonists of airway smooth muscle and can act via two different ET receptor subtypes, i.e., ET A and ET B . To determine the effects of ET-1 on in vivo pulmonary function and which ET receptors are involved in murine lungs, we investigated 1) the effects of ET and sarafotoxin S6c (S6c), a selective ET B agonist, on pulmonary function and 2) the effects of BQ-123 and BQ-788, specific ET A - and ET B -receptor antagonists, on ET-1-induced bronchoconstriction. ICR mice were anesthetized and mechanically ventilated (frequency = 2.5 Hz, tidal volume = 8 ml/kg, positive end-expiratory pressure = 3 cmH 2 O). Intravenous ET-1, ET-2, and ET-3 increased lung resistance similarly and equipotently, whereas S6c elicited a greater degree of bronchoconstriction. Mice were then pretreated with saline (Sal), BQ-123 (0.2, 1, and 5 mg/kg), or BQ-788 (0.2, 1, and 5 mg/kg) before administration of ET-1 (10 −7 mol/kg iv). No dose of BQ-123 blocked ET-1-induced constriction, whereas pretreatment with each dose of BQ-788 significantly inhibited ET-1-induced responses. There were significant differences in morphometrically assessed airway constriction between Sal and BQ-788 and between BQ-123 and BQ-788, whereas no significant difference was observed between Sal and BQ-123. There were no significant morphometric differences in the airway wall area among the three groups. These observations suggest that the ET B - but not ET A -receptor subtype may mediate the changes in murine pulmonary function in response to ET-1. In addition, the ET B -receptor antagonist reduces ET-1-induced airway narrowing by affecting airway smooth muscle contraction in mice.
Type of Medium:
Online Resource
ISSN:
8750-7587
,
1522-1601
DOI:
10.1152/jappl.1997.83.1.46
Language:
English
Publisher:
American Physiological Society
Publication Date:
1997
detail.hit.zdb_id:
1404365-8
SSG:
12
SSG:
31
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