Endothelin receptor antagonists in pulmonary arterial hypertension

J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):62S-67S. doi: 10.1016/j.jacc.2004.02.042.


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.

Publication types

  • Review

MeSH terms

  • Endothelin Receptor Antagonists*
  • Endothelin-1 / drug effects
  • Endothelin-1 / metabolism
  • Forecasting
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / metabolism
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / pathology*
  • Randomized Controlled Trials as Topic


  • Endothelin Receptor Antagonists
  • Endothelin-1