title: Endothelin receptor antagonists for the treatment of pulmonary arterial hypertension.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, F 94276, France.
authors.forename: Dermot S
authors.initials: DS
authors.lastname: O'Callaghan
authors.forename: Laurent
authors.initials: L
authors.lastname: Savale
authors.forename: Azzedine
authors.initials: A
authors.lastname: Yaïci
authors.forename: Delphine
authors.initials: D
authors.lastname: Natali
authors.forename: Xavier
authors.initials: X
authors.lastname: Jaïs
authors.forename: Florence
authors.initials: F
authors.lastname: Parent
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077300:Bosentan; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D010666:Phenylpropionates / Q000494:pharmacology / Q000627:therapeutic use; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; D013449:Sulfonamides; C467894:ambrisentan; D000077300:Bosentan