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 mu g 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.
Endothelin-1 induced bronchial hyperresponsiveness in the rabbit: an ETA receptor-mediated phenomenon / D'Agostino, B., Gallelli, L., Falciani, M., DI PIERRO, P., Rossi, F., Filippelli, A., Rossi, F.. - In: NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY. - ISSN 0028-1298. - STAMPA. - 360:6(1999), pp. 665-669. [10.1007/s002109900146]
Endothelin-1 induced bronchial hyperresponsiveness in the rabbit: an ETA receptor-mediated phenomenon
DI PIERRO, PROSPERO;
1999
Abstract
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 mu g 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
