关键词: 内皮素受体拮抗剂, 内皮素受体, 放射受体分析, 肺动脉高压, 低氧, 血流动力学

Abstract: AIM: To investigate the affinity and selectivity of endothelin antagonist darusentan on the ET_A and ET_B receptor of rat left ventricle and its effect on the hemodynamic parameters in hypoxia-induced pulmonary hypertensive rat.METHODS: Radio receptor binding assay method was used to determine the competition binding of darusentan.Pulmonary hypertensive rats were induced by hypoxia.A multiple physiological recorder was used to record the hemodynamic parameters.RESULTS: The competition binding of¹²⁵ I-ET1 to ETR at darusentan 0.1μmol·L^-1 presence was 31.50%±7.7%.The IC₅₀ to suppress ETA and ETB of darusentan was 1.93±0.21and 147±20μmol·L^-1.It was 76.16 fold of selectivity for the ET_A receptor over the ET_B receptor.By 28 d of exposure to hypoxia,rats had already developed significant pulmonary hypertension as estimated by increased right ventricle systolic pressure (RVSP),right ventricle end diastolic pressure (RVEDP),right ventricle +dp/dtmax and-dp/dt min.Once treatment with darusentan by ivinjection,pulmonary hypertensive changes were significantly reducad in the right ventricle.CONCLUSION: Darusentan has significantly antagonistic effects on the left ventricle membrane and has high selectivity for ETAR.It effectively ameliorates the hemodynamic parameters in hypoxia-induced pulmonary hypertensive rats.

Key words: endothelin receptor antagonists, endothelin receptor, radio receptor assay, pulmonary hypertension, hypoxia, hemodynamic parameters