Plasma tetrahydrobiopterin/dihydrobiopterin ratio - A possible marker of endothelial dysfunction

Masafumi Takeda, Tomoya Yamashita, Masakazu Shinohara, Naoto Sasaki, Tomofumi Takaya, Kenji Nakajima, Nobutaka Inoue, Tomoya Masano, Hideto Tawa, Seimi Satomi-Kobayashi, Ryuji Toh, Daisuke Sugiyama, Kunihiro Nishimura, Mitsuhiro Yokoyama, Ken Ichi Hirata, Seinosuke Kawashima

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)


Background: Although endothelium-dependent vasodilatation has been used as a marker of endothelial dysfunction (ED), there have been no reliable plasma markers for ED. Oxidative stress, which is a major determinant of ED, oxidizes tetrahydrobiopterin (BH4), an essential cofactor of endothelial type nitric oxide synthase (eNOS), and resulted in the relative deficiency of BH4. Methods and Results: In 163 patients with cardiovascular disorders, the plasma levels of BH4 and 7, 8-dihydrobiopterin (BH2) by high performance liquid chromatography were measured and compared with the flow-mediated (FMD) vasodilatory response of the brachial artery, which was measured by ultrasonography. The effects of atorvastatin on plasma pteridine levels and FMD were examined in patients with multiple coronary risk factors. There was a positive relationship between FMD and plasma BH4 levels and a negative relationship between FMD and plasma BH2 levels. Subsequently, a strong positive relationship between FMD and the BH4/BH2 ratio (r=0.585, P<0.0001) was found. Although we did not find any significant relationship between pteridine levels and individual traditional risk factors, the BH4/BH2 ratio in patients with more than 2 risk factors showed significant reductions compared with that in those without risk factors. Statin treatment improved FMD in association with an increase in the plasma BH4/BH2 ratio. Conclusions: Plasma pteridine levels were associated with endothelial dysfunction in cardiovascular disorders.

Original languageEnglish
Pages (from-to)955-962
Number of pages8
JournalCirculation Journal
Issue number5
Publication statusPublished - 2009 May
Externally publishedYes


  • Endothelial dysfunction
  • FMD
  • Plasma pteridine level
  • Statin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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