Endothelin-1 induced bronchial hyperresponsiveness in the rabbit: an ETA receptor-mediated phenomenon
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- D'Agostino, B., Gallelli, L., Falciani, M. et al. Naunyn-Schmiedeberg's Arch Pharmacol (1999) 360: 665. doi:10.1007/s002109900146
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Endothelin-1 (ET-1) is a potent and efficacious spasmogen of airway smooth muscle. Recent observations suggest that an increased intrapulmonary production of ET-1 may occur in asthma. Our previous study showed that endothelin-1 induced bronchial hyperresponsiveness to inhaled histamine in the rabbit. The aim of this study was to investigate whether the ETA and ETB receptors mediate the bronchial hyperresponsiveness induced by endothelin-1 in the rabbit.
Our data showed that bronchial hyperresponsiveness induced by ET-1 was significantly inhibited (P<0.01) by the ETA receptor-selective antagonist, FR 139317 (from 2.5 to 10 mg kg–1). Moreover, bosentan (from 2.5 mg kg–1 to 10 mg kg–1), an ETA/ETB receptor antagonist, also inhibited the bronchial hyperresponsiveness achieved 24 h following endothelin-1 challenge (P<0.01), but with no difference from FR 139317. The ETB receptor agonist, sarafotoxin S6c (from 25 µg to 2.5 mg kg–1) did not modify airway responsiveness to inhaled histamine in the rabbit.
These results indicate that bronchial hyperresponsiveness induced by ET-1 may be mediated by ETA receptor activation.