Plasma tetrahydrobiopterin/dihydrobiopterin ratio: a possible marker of endothelial dysfunction.
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.
Takeda
Masafumi
M
Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Yamashita
Tomoya
T
Shinohara
Masakazu
M
Sasaki
Naoto
N
Takaya
Tomofumi
T
Nakajima
Kenji
K
Inoue
Nobutaka
N
Masano
Tomoya
T
Tawa
Hideto
H
Satomi-Kobayashi
Seimi
S
Toh
Ryuji
R
Sugiyama
Daisuke
D
Nishimura
Kunihiro
K
Yokoyama
Mitsuhiro
M
Hirata
Ken-ichi
K
Kawashima
Seinosuke
S
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
D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D001708:Biopterins; C017226:7,8-dihydrobiopterin; D000069059:Atorvastatin; C003402:sapropterin