Clinical Pharmacology of Endothelin Receptor Antagonists Used in the Treatment of Pulmonary Arterial Hypertension

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• 作者：Marie-Camille Chaumais (1) (2) (3)
  Christophe Guignabert (2)
  Laurent Savale (2) (5)
  Xavier Ja茂s (2) (5)
  Ath茅na茂s Boucly (5)
  David Montani (2) (4) (5)
  G茅rald Simonneau (2) (4) (5)
  Marc Humbert (2) (4) (5)
  Olivier Sitbon (2) (4) (5) (6)
  
  1. Facult茅 de Pharmacie ; Univ. Paris-Sud ; Ch芒tenay Malabry ; France
  2. INSERM UMR_S 999 ; LabEx LERMIT ; Centre Chirurgical Marie Lannelongue ; Le Plessis-Robinson ; France
  3. AP-HP ; Service de Pharmacie ; D茅partement Hospitalo-Universitaire (DHU) Thorax Innovation ; H么pital Antoine B茅cl猫re ; Clamart ; France
  5. AP-HP ; Centre de R茅f茅rence de l鈥橦ypertension Pumonaire S茅v猫re ; D茅partement Hospitalo-Universitaire (DHU) Thorax Innovation ; Service de Pneumologie et ; H么pital Bic锚tre ; Le Kremlin-Bic锚tre ; France
  4. Facult茅 de M茅decine ; Univ. Paris-Sud ; Le Kremlin-Bic锚tre ; France
  6. Service de Pneumologie et Soins Intensifs ; H么pital Universitaire de Bic锚tre ; 78 ; rue du G茅n茅ral Leclerc ; 94270 ; Le Kremlin-Bic锚tre ; France
  
• 刊名：American Journal of Cardiovascular Drugs
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：15
• 期：1
• 页码：13-26
• 全文大小：782 KB
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• 刊物主题：Cardiology; Pharmacotherapy; Pharmacology/Toxicology;
• 出版者：Springer International Publishing
• ISSN：1179-187X

文摘

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.