Role of endothelin ETB receptors in bronchoconstrictor and vasoconstrictor responses in guinea-pigs.

In anesthetized and ventilated guinea-pigs, intravenous injections of endothelin (ET)-1 (0.5 nmol/kg), ET-3 (0.5 nmol/kg), and [Ala1,3,11,15]ET-1 (20 nmol/kg), an ETB-selective receptor agonist, induced bronchoconstrictor and transient vasoconstrictor responses. Only the ET-1-induced transient vasoconstriction was followed by a secondary sustained pressor response. The ETA-selective receptor antagonist, BQ-123 (1 mg/kg i.v.), attenuated only the sustained pressor response. These results indicate that the bronchoconstrictor and transient vasoconstrictor responses to endothelins in guinea-pigs are mediated by ETB receptors, whilst the sustained pressor response is mediated by ETA receptors. The thromboxane A2 receptor antagonist, L-670,596 (0.5 mg/kg, i.v.) and a high dose of BQ-123 (30 mg/kg i.v.) abolished the bronchoconstriction only without affecting the transient pressor response to endothelin isopeptides. These results suggest that the ETB-mediated bronchoconstriction depends on thromboxane A2 formation. The different sensitivity of these ETB-mediated transient responses to BQ-123 suggests the possible existence of distinct ETB receptor subtypes.