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J Appl Physiol 83: 46-51, 1997;
8750-7587/97 $5.00
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Journal of Applied Physiology
Vol. 83, No. 1, pp. 46-51, July 1997
GAS EXCHANGE, MECHANICS, AND AIRWAYS

ET-1-induced bronchoconstriction is mediated via ETB receptor in mice

Takahide Nagase, Tomoko Aoki, Teruaki Oka, Yoshinosuke Fukuchi, and Yasuyoshi Ouchi

Department of Geriatrics and Department of Pathology, Faculty of Medicine, University of Tokyo, Tokyo 113; and Imperial Household Agency, Tokyo 100, Japan

Received 10 October 1996; accepted in final form 4 March 1997.

Nagase, Takahide, Tomoko Aoki, Teruaki Oka, Yoshinosuke Fukuchi, and Yasuyoshi Ouchi. ET-1-induced bronchoconstriction is mediated via ETB 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., ETA and ETB. 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 ETB agonist, on pulmonary function and 2) the effects of BQ-123 and BQ-788, specific ETA- and ETB-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 cmH2O). 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 ETB- but not ETA-receptor subtype may mediate the changes in murine pulmonary function in response to ET-1. In addition, the ETB-receptor antagonist reduces ET-1-induced airway narrowing by affecting airway smooth muscle contraction in mice.

BQ-123; BQ-788; airway resistance; wild-type mice; endothelin-1; endothelinA receptors; endothelinB receptors

0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society




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