Endothelin receptor antagonists for the treatment of pulmonary arterial hypertension

Expert Opin Pharmacother. 2011 Jul;12(10):1585-96. doi: 10.1517/14656566.2011.564159. Epub 2011 Apr 20.

Abstract

Introduction: Endothelin is a key mediator in the pathophysiology of pulmonary arterial hypertension (PAH). Its effects are mediated through the activation of two associated receptor subtypes, termed A and B. Therapeutic strategies that modulate the activity of endothelin are, therefore, of interest to improve the functional status of patients with PAH.

Areas covered: The rationale for the use of endothelin receptor antagonists as a therapeutic class in PAH and pertinent data from important clinical studies are presented in this review. Areas for future research are also suggested.

Expert opinion: The availability of the endothelin receptor antagonist class of agents represents a significant addition to the therapeutic armamentarium which is available for the treatment of PAH. Comparative studies are warranted to establish whether selective endothelin-A receptor antagonism is more advantageous than dual receptor antagonism. Future studies of endothelin receptor antagonists will increasingly focus on the potential of a combination of different PAH therapeutic classes and will employ 'harder' clinical end points. This is of crucial importance to ensure that future developments are both worthwhile and acceptable to patients, physicians, health system payers and regulatory authorities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Bosentan
  • Endothelin A Receptor Antagonists*
  • Endothelin B Receptor Antagonists*
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Phenylpropionates / pharmacology
  • Phenylpropionates / therapeutic use
  • Pyridazines / pharmacology
  • Pyridazines / therapeutic use
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use

Substances

  • Antihypertensive Agents
  • Endothelin A Receptor Antagonists
  • Endothelin B Receptor Antagonists
  • Phenylpropionates
  • Pyridazines
  • Sulfonamides
  • ambrisentan
  • Bosentan