title: Clinical pharmacology of endothelin receptor antagonists used in the treatment of pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a devastating life-threatening disorder characterized by elevated pulmonary vascular resistance leading to elevated pulmonary arterial pressures, right ventricular failure, and ultimately death. Vascular endothelial cells mainly produce and secrete endothelin (ET-1) in vessels that lead to a potent and long-lasting vasoconstrictive effect in pulmonary arterial smooth muscle cells. Along with its strong vasoconstrictive action, ET-1 can promote smooth muscle cell proliferation. Thus, ET-1 blockers have attracted attention as an antihypertensive drug, and the ET-1 signaling system has paved a new therapeutic avenue for the treatment of PAH. We outline the current understanding of not only the pathogenic role played by ET-1 signaling systems in the pathogenesis of PH but also the clinical pharmacology of endothelin receptor antagonists (ERA) used in the treatment of PAH.
authors.affiliation: Faculté de Pharmacie, Univ. Paris-Sud, Châtenay Malabry, France.
authors.forename: Marie-Camille
authors.initials: MC
authors.lastname: Chaumais
authors.forename: Christophe
authors.initials: C
authors.lastname: Guignabert
authors.forename: Laurent
authors.initials: L
authors.lastname: Savale
authors.forename: Xavier
authors.initials: X
authors.lastname: Jaïs
authors.forename: Athénaïs
authors.initials: A
authors.lastname: Boucly
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects; D065128:Endothelin Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017410:Practice Guidelines as Topic; D011652:Pulmonary Circulation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014657:Vasculitis / Q000209:etiology / Q000517:prevention & control
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D016232:Endothelins