Tetrahydrobiopterin improves endothelial function in human saphenous veins

Objectives: Diminished production of nitric oxide has been linked to saphen ous vein endothelial dysfunction. Tetrahydrobiopterin is an obligate cofact or for the oxidation of L-arginine by nitric oxide synthase in the producti on of nitric oxide by endothelial cells. The objective of the present study was to examine whether the exogenous addition of tetrahydrobiopterin impro ves endothelial function in saphenous veins from patients undergoing corona ry artery bypass graft operations. Methods: Vascular segments of saphenous veins were obtained from 17 patient s undergoing elective coronary artery bypass grafting, and in vitro endothe lium-dependent and endothelium-independent responses to acetylcholine and s odium nitroprusside were assessed. Isometric dose;response curves were cons tructed in precontracted rings in the presence and absence of tetrahydrobio pterin (0.1 mmol/L) with the use of the organ bath apparatus. The percentag es of maximum relaxation and sensitivity were compared between intervention s. Results: Acetylcholine caused dose-dependent endothelium-mediated relaxatio n in saphenous veins. In the presence of tetrahydrobiopterin, acetylcholine -induced relaxation was significantly augmented (percentage maximum relaxat ion, 16.8% +/- 2.9% vs control 7.5% +/- 1.8%; P =.003) without an effect on agonist sensitivity. These effects were endothelium-specific because endot helium-independent responses to sodium nitroprusside were preserved. Conclusions: These data uncover beneficial effects of acute tetrahydrobiopt erin addition on endothelial function in human vessels. Because endothelial dysfunction has been implicated in the development of graft failure, studi es aimed at chronic delivery of tetrahydrobiopterin would be useful in dete rmining the contribution of this cofactor toward saphenous vein atheroscler osis.