title: Endothelin receptor antagonists in pulmonary arterial hypertension.
abstract: Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension (PAH). Laboratory and clinical investigations have clearly shown that endothelin (ET)-1 is overexpressed in several forms of pulmonary vascular disease and likely plays a significant pathogenetic role in the development and progression of pulmonary vasculopathy. Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials. In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil. The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation.
authors.affiliation: Pulmonary and Critical Care Division, University of California, San Diego, California, USA. rchannick@ucsd.edu
authors.forename: Richard N
authors.initials: RN
authors.lastname: Channick
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.forename: Alessandra
authors.initials: A
authors.lastname: Manes
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
mesh_terms: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism; D005544:Forecasting; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1