Article Text

Download PDFPDF
Tetrahydrobiopterin: pleiotropic roles in cardiovascular pathophysiology
  1. Colin Cunnington,
  2. Keith M Channon
  1. Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
  1. Correspondence to Professor Keith M Channon, Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; keith.channon{at}


Tetrahydrobiopterin (BH4) functions as a cofactor in several important enzyme systems. Substantial evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of endothelial dysfunction and atherosclerosis. Investigators have now taken early steps in addressing the potential of BH4 as a therapeutic strategy. However, it has become more apparent that the role of BH4 in other enzymatic pathways, including other NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on important aspects of cardiovascular homeostasis. Together with eNOS, these enzymes may play key roles in diverse cardiovascular disease states such as ischaemia-reperfusion injury, cardiac hypertrophy, cardiac autonomic function and pulmonary hypertension. This review provides an overview of the role of BH4 in cardiovascular pathophysiology.

  • Tetrahydrobiopterin
  • nitric oxide synthase
  • endothelium
  • cardiovascular system
  • autonomic regulation
  • coronary artery disease (CAD)
  • nitric oxide

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Funding Work in the authors' laboratory is supported by the British Heart Foundation (grants RG/07/003/23133 and PG/08/119/26263) and by the NIHR Oxford Biomedical Research Centre.

  • Competing interests The authors are investigators in the OXBIO study (NCT00423280) of oral BH4 treatment, supported by BioMarin Pharmaceutical Inc.

  • Provenance and peer review Commissioned; externally peer reviewed.