Bosentan, an ET-1 antagonist, obviously blunted the increase of sPAP induced by acute hypoxic exposure.235,236 However, its use requires caution due to decreased urinary volume and free water clearance.235 These results indicate that the prophylactic benefits of ET-1 antagonism against altitude-induced pulmonary hypertension may be accompanied by impaired volume adaptation. This evidence concerns the gene EDN1 and pulmonary hypertension.