Endothelin-1 induced bronchial hyperresponsiveness in the rabbit: an ETA receptor-mediated phenomenon

Endothelin-1 (ET-1) is a potent and efficacious spasmogen of airway smooth muscle. Recent observations suggest that an increased intrapulmonary produc tion 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 receptor s mediate the bronchial hyperresponsiveness induced by endothelin-1 in the rabbit. Our data showed that bronchial hyperresponsiveness induced by ET-1 was sign ificantly inhibited (P<0.01) by the ETA receptor-selective antagonist, FR 1 39317 (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 bronchia l hyperresponsiveness achieved 24 h following endothelin-1 challenge (P<0.0 1), but with no difference from FR 139317. The ETB receptor agonist, sarafo toxin S6c (from 25 mu g to 2.5 mg kg(-1)) did not modify airway responsiven ess to inhaled histamine in the rabbit. These results indicate that bronchial hyperresponsiveness induced by ET-1 m ay be mediated by ETA receptor activation.