ET-1-induced pulmonary vasoconstriction shifts from ETA- to ETB-receptor-mediated reaction after preconstriction

Department of Anesthesiology and Operative Intensive Care Medicine, University Hospital Mannheim, University of Heidelberg, 68135 Mannheim, Germany Endothelin-1 (ET-1) has been reported to induce pulmonary vasoconstriction via either ET A or ET B receptors, and vasorelaxation after ET-1 injection has been observed. Our study investigated the effects of ET-1 in isolated rabbit lungs, which were studied at basal tone ( part I ) and after preconstriction (U-46619; part II ). Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. In part I , ET-1 (10 8 M; n = 6; control) was injected after pretreatment with the ET A -receptor antagonist BQ-123 (10 6 M; n = 6) or the ET B -receptor antagonist BQ-788 (10 6 M; n = 6). The same protocol was carried out in part II after elevation of pulmonary vascular tone. ET-1 induced an immediate PAP increase ( PAP 4.3 ± 0.4 mmHg at 10 min) that was attenuated by pretreatment with BQ-123 ( P