Tetrahydrobiopterin restores endothelial function of coronary arteries in patients with hypercholesterolaemia.
OBJECTIVE
To examine the effect of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase, on coronary artery endothelial function in hypercholesterolaemic patients.


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


METHODS
Tertiary cardiology centre.


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


METHODS
ACh (3 and 30 microg/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 micromol/min for five minutes).


METHODS
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.
Fukuda
Y
Y
First Department of Internal Medicine, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. yfukuda@hiroshima-u.ac.jp
Teragawa
H
H
Matsuda
K
K
Yamagata
T
T
Matsuura
H
H
Chayama
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D001708:Biopterins; D019323:omega-N-Methylarginine; C003402:sapropterin; D005996:Nitroglycerin; D000109:Acetylcholine