title: Plasma tetrahydrobiopterin/dihydrobiopterin ratio: a possible marker of endothelial dysfunction.
abstract: 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.
  
  
  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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeda
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shinohara
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Takaya
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakajima
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Inoue
authors.forename: Tomoya
authors.initials: T
authors.lastname: Masano
authors.forename: Hideto
authors.initials: H
authors.lastname: Tawa
authors.forename: Seimi
authors.initials: S
authors.lastname: Satomi-Kobayashi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Toh
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Nishimura
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Kawashima
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001708:Biopterins / Q000031:analogs & derivatives* / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011758:Pyrroles / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D001708:Biopterins; C017226:7,8-dihydrobiopterin; D000069059:Atorvastatin; C003402:sapropterin