查看文章

Objective

Macitentan is a dual endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension (PAH). We evaluated the efficacy of two different treatment protocols with macitentan (supplemented in food) in a translationally relevant rat model of PAH. METHODS AND RESULTS: Male Sprague-Dawley rats received Sugen5416 prior to 3 weeks of hypoxia (Hx, 10% of oxygen) followed by normoxia (Nx). Two separate protocols of 3-week treatments with macitentan were applied, namely ‘early’and ‘late’interventional protocol. Baseline assessment of PAH by using ultrasound analysis (Vevo3100 Fujifilm Visualsonics) was performed 24h after returning to Nx for ‘early protocol’and 3 weeks after for ‘late interventional protocol’. Treatment started 48h and 3 weeks after returning to Nx, respectively. For both protocols, the groups were: 1) Sugen/Hypoxia (SUHx) rats receiving vehicle; 2) SUHx …