BASIC RESEARCH

Tetrahydrobiopterin restores endothelial function of coronary arteries in patients with hypercholesterolaemia

Y Fukuda, H Teragawa, K Matsuda, T Yamagata, H Matsuura, K Chayama

First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734–8551, Japan

Correspondence to:
Correspondence to:
Dr Yukihiro Fukuda, First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734–8551, Japan;
yfukuda{at}hiroshima-u.ac.jp

Objective: To examine the effect of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase, on coronary artery endothelial function in hypercholesterolaemic patients.

Design: Quantitative coronary angiography and Doppler flowmetry were used to examine the effects of intracoronary infusion of BH4 on vascular response to acetylcholine (ACh).

Setting: Tertiary cardiology centre.

Patients: 18 patients with angiographically normal coronary arteries, of whom nine had hypercholesterolaemia and nine had noromocholesterolaemia.

Interventions: ACh (3 and 30 µg/min) was infused for two minutes into the left coronary ostium. ACh was then simultaneously infused with BH4 (1 mg/min) before and after infusion of L-N^G-monomethyl-L-arginine (L-NMMA) (40 µmol/min for five minutes).

Main outcome measures: Diameter of the epicardial coronary arteries and coronary blood flow.

Results: In hypercholesterolaemic patients, BH4 attenuated the ACh induced decrease in coronary diameter (p < 0.05) and restored the ACh induced increase in coronary blood flow (p < 0.05). In normocholesterolaemic patients, BH4 did not affect the ACh induced changes in coronary diameter or coronary blood flow. In both groups, L-NMMA decreased the baseline coronary diameter (p < 0.05) and baseline coronary blood flow (p < 0.05). In hypercholesterolaemic patients, L-NMMA inhibited both the BH4 mediated attenuation of the ACh induced decrease in coronary diameter (p < 0.05) and the BH4 mediated enhancement of the ACh induced increase in coronary blood flow (p < 0.01).

Conclusions: Intracoronary infusion of BH4 restores coronary endothelial function by improving the bioavailability of endothelium derived nitric oxide in hypercholesterolaemic patients.

Keywords: coronary artery; tetrahydrobiopterin; nitric oxide; hypercholesterolaemia

Abbreviations: ACh, acetylcholine; BH4, tetrahydrobiopterin; L-NMMA, L-N^G-monomethyl-L-arginine

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