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. 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 hypercholesterolaemio and nine had noromocholesterolaemia. Interventions: ACh (3 and 30 mug/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 mumol/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.