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J Thorac Cardiovasc Surg 2000;120:668-671
© 2000 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

Tetrahydrobiopterin improves endothelial function in human saphenous veins

From the Divisions of Cardiology,^a Pharmacology,^b and Cardiac Surgery,^c Faculty of Medicine, The University of Calgary, Calgary, Alberta, Canada.

Supported by grants from the Heart and Stroke Foundation of Canada (T.J.A., C.R.T.) and the Medical Research Council of Canada (C.R.T.). S.V. and K.J.M. are Alberta Heritage for Medical Research (AHFMR) Fellows. A.D. holds an AHFMR studentship. T.J.A. is a Clinical Investigator of the AHFMR.

Address for reprints: Todd J. Anderson, MD, FRCPC, Associate Professor of Medicine, Division of Cardiology, Foothills Hospital, 1403 29th St, NW, Calgary, Alberta, T2N 2T9 Canada (E-mail: todd.anderson{at}CRHA-health.ab.ca).

Objectives: Diminished production of nitric oxide has been linked to saphenous vein endothelial dysfunction. Tetrahydrobiopterin is an obligate cofactor for the oxidation of L-arginine by nitric oxide synthase in the production of nitric oxide by endothelial cells. The objective of the present study was to examine whether the exogenous addition of tetrahydrobiopterin improves endothelial function in saphenous veins from patients undergoing coronary artery bypass graft operations.
Methods: Vascular segments of saphenous veins were obtained from 17 patients undergoing elective coronary artery bypass grafting, and in vitro endothelium-dependent and endothelium-independent responses to acetylcholine and sodium nitroprusside were assessed. Isometric dose-response curves were constructed in precontracted rings in the presence and absence of tetrahydrobiopterin (0.1 mmol/L) with the use of the organ bath apparatus. The percentages of maximum relaxation and sensitivity were compared between interventions.
Results: Acetylcholine caused dose-dependent endothelium-mediated relaxation in saphenous veins. In the presence of tetrahydrobiopterin, acetylcholine-induced relaxation was significantly augmented (percentage maximum relaxation, 16.8% ± 2.9% vs control 7.5% ± 1.8%; P = .003) without an effect on agonist sensitivity. These effects were endothelium-specific because endothelium-independent responses to sodium nitroprusside were preserved.
Conclusions: These data uncover beneficial effects of acute tetrahydrobiopterin addition on endothelial function in human vessels. Because endothelial dysfunction has been implicated in the development of graft failure, studies aimed at chronic delivery of tetrahydrobiopterin would be useful in determining the contribution of this cofactor toward saphenous vein atherosclerosis.

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