Hemodynamic Effects of Bosentan, an Endothelin Receptor Antagonist, in Patients With Pulmonary Hypertension

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Abstract
Background—Few treatments are available for isolated pulmonary hypertension (PHT), which has a high morbidity and mortality. This trial was designed to assess the hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with PHT, in which local overproduction of endothelin-1 (ET-1) is thought to play a pathogenic role. Methods and Results—An open-label, dose-ranging study was performed in 7 female patients with primary PHT (n=5) or isolated PHT associated with limited scleroderma (n=2). Infusions of 50, 150, and 300 mg were administered at 2-hour intervals, and the hemodynamic responses were measured. Bosentan caused a dose-dependent fall in total pulmonary resistance (−20.0±11.0%, P=0.01) and mean pulmonary artery pressure (−10.6±11.0%, P>0.05). However, there was also a fall in the systemic vascular resistance (−26.2±12.8%, P<0.005) and mean arterial pressure (−19.8±14.4%, P0.05) and a dose-dependent rise in ET-1 but...