Endothelin receptor antagonists for the treatment of pulmonary artery hypertension

Life Sci. 2012 Oct 15;91(13-14):517-21. doi: 10.1016/j.lfs.2012.07.033. Epub 2012 Aug 3.


Aims: The demonstration that endothelin production is upregulated in pulmonary artery hypertension (PAH) served as the rationale for developing endothelin-receptor antagonists (ERAs) as a treatment for PAH. This article reviews the primary studies demonstrating efficacy of ERAs in PAH.

Main methods: Multicenter, placebo-controlled trials and open-label extension studies.

Key findings: Two orally active ERAs are currently approved for the treatment of PAH - the dual receptor antagonist bosentan, and the more selective ET(A) receptor antagonist ambrisentan-based on multicenter randomized clinical trials demonstrating efficacy and safety. Long-term experience with both agents supports maintenance of therapeutic effects in most patients. Adverse effects, including altered liver function and edema may occur and require careful monitoring.

Significance: Despite failure to demonstrate efficacy of ERAs in other cardiopulmonary conditions, ERAs have a major role in the treatment algorithm for PAH.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Bosentan
  • Drug Design
  • Drug Monitoring
  • Endothelin Receptor Antagonists*
  • Endothelin-1 / metabolism
  • Familial Primary Pulmonary Hypertension
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Phenylpropionates / administration & dosage
  • Phenylpropionates / pharmacology
  • Phenylpropionates / therapeutic use
  • Pyridazines / administration & dosage
  • Pyridazines / pharmacology
  • Pyridazines / therapeutic use
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use


  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Phenylpropionates
  • Pyridazines
  • Sulfonamides
  • ambrisentan
  • Bosentan