Therapeutic targets in pulmonary arterial hypertension

Pharmacol Ther. 2009 Jan;121(1):69-88. doi: 10.1016/j.pharmthera.2008.10.002. Epub 2008 Oct 28.


Pulmonary arterial hypertension is a progressive, fatal disease. Current treatments including prostanoids, endothelin-1 (ET-1) antagonists, and phosphodiesterase (PDE) inhibitors, have sought to address the pulmonary vascular endothelial dysfunction and vasoconstriction associated with the condition. These treatments may slow the progression of the disease but do not afford a cure. Future treatments must target more directly the structural vascular changes that impair blood flow through the pulmonary circulation. Several novel therapeutic targets have been proposed and are under active investigation, including soluble guanylyl cyclase, phosphodiesterases, tetrahydrobiopterin, 5-HT2B receptors, vasoactive intestinal peptide, receptor tyrosine kinases, adrenomedullin, Rho kinase, elastases, endogenous steroids, endothelial progenitor cells, immune cells, bone morphogenetic protein and its receptors, potassium channels, metabolic pathways, and nuclear factor of activated T cells. Tyrosine kinase inhibitors, statins, 5-HT2B receptor antagonists, EPCs and soluble guanylyl cyclase activators are among the most advanced, having produced encouraging results in animal models, and human trials are underway. This review summarises the current research in this area and speculates on their likely success.

Publication types

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

MeSH terms

  • Adrenomedullin / pharmacology
  • Adrenomedullin / therapeutic use
  • Animals
  • Bone Morphogenetic Protein Receptors / drug effects
  • Bone Morphogenetic Protein Receptors / metabolism
  • Cyclic GMP / metabolism
  • Cyclic GMP / pharmacology*
  • Cyclic GMP / physiology*
  • Dichloroacetic Acid / pharmacology
  • Dichloroacetic Acid / therapeutic use
  • Drug Discovery*
  • Endothelial Cells
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology*
  • NFATC Transcription Factors / drug effects
  • NFATC Transcription Factors / metabolism
  • Pancreatic Elastase / antagonists & inhibitors
  • Pancreatic Elastase / drug effects
  • Pneumonia / drug therapy
  • Pneumonia / physiopathology
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology
  • Serotonin / pharmacology
  • Serotonin / physiology
  • Stem Cells / metabolism
  • Vasoactive Intestinal Peptide / pharmacology
  • Vasoactive Intestinal Peptide / therapeutic use
  • rho-Associated Kinases / antagonists & inhibitors


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • NFATC Transcription Factors
  • Adrenomedullin
  • Serotonin
  • Vasoactive Intestinal Peptide
  • Dichloroacetic Acid
  • Receptor Protein-Tyrosine Kinases
  • rho-Associated Kinases
  • Bone Morphogenetic Protein Receptors
  • Pancreatic Elastase
  • Cyclic GMP