Clinical pharmacology of endothelin receptor antagonists used in the treatment of pulmonary arterial hypertension

Am J Cardiovasc Drugs. 2015 Feb;15(1):13-26. doi: 10.1007/s40256-014-0095-y.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / pharmacokinetics
  • Antihypertensive Agents / therapeutic use*
  • Drug Interactions
  • Drug Therapy, Combination / adverse effects
  • Endothelin Receptor Antagonists / adverse effects
  • Endothelin Receptor Antagonists / pharmacokinetics
  • Endothelin Receptor Antagonists / therapeutic use*
  • Endothelins / antagonists & inhibitors
  • Endothelins / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / immunology
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / physiopathology
  • Models, Biological*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / immunology
  • Muscle, Smooth, Vascular / metabolism
  • Practice Guidelines as Topic
  • Pulmonary Circulation / drug effects
  • Signal Transduction / drug effects
  • Vasculitis / etiology
  • Vasculitis / prevention & control

Substances

  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Endothelins