In vivo effects of endothelin A- and B-receptor antagonists in guinea pigs

摘要: Endothelin (ET)-1, a novel 21-amino acid constrictor peptide, has been recently reported to have potential pathophysiological role in asthma. We hypothesized that ET-1 might affect guinea pig lung via different ET receptor subtypes, i.e., ETA and ETB, vivo. To test this hypothesis, we investigated the effects of on airways anesthetized, open-chest, mechanically ventilated [frequency (f) = 1 Hz; tidal volume (VT) 9 ml/kg; positive end-expiratory pressure (PEEP) 4 cmH2O] pigs absence or presence ETB selective antagonists, BQ-123 BQ-788, respectively. affixed alveolar capsules lungs measure calculated elastance (EL) resistance (RL), tissue (Rti), airway (R(aw)) under control conditions after intravenous administration (10(-8) mol/kg). induced concentration-dependent increase RL, Rti, R(aw), EL.BQ-123 (2 mg/kg) partially blocks delta RL R(aw) during constriction, while Rti EL were not significantly affected. BQ-788 inhibited ET-1-induced constriction. The combination completely ablated response ET-1. These data suggest both may physiological roles ET-1, mediator