Tetrahydrobiopterin improves endothelial function in human saphenous veins

Subodh Verma, Fina Lovren, Aaron S. Dumont, Kieren J. Mather, Andrew Maitland, Teresa M. Kieser, Christopher Triggle, Todd J. Anderson

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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 tetrahydro-biopterin 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.

Original languageEnglish
Pages (from-to)668-671
Number of pages4
JournalJournal of Thoracic and Cardiovascular Surgery
Volume120
Issue number4
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Saphenous Vein
Endothelium
Acetylcholine
Nitroprusside
Coronary Artery Bypass
Nitric Oxide
Biopterin
Transplants
Baths
Nitric Oxide Synthase
Blood Vessels
Arginine
Atherosclerosis
Endothelial Cells
sapropterin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Verma, S., Lovren, F., Dumont, A. S., Mather, K. J., Maitland, A., Kieser, T. M., ... Anderson, T. J. (2000). Tetrahydrobiopterin improves endothelial function in human saphenous veins. Journal of Thoracic and Cardiovascular Surgery, 120(4), 668-671.

Tetrahydrobiopterin improves endothelial function in human saphenous veins. / Verma, Subodh; Lovren, Fina; Dumont, Aaron S.; Mather, Kieren J.; Maitland, Andrew; Kieser, Teresa M.; Triggle, Christopher; Anderson, Todd J.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 120, No. 4, 2000, p. 668-671.

Research output: Contribution to journalArticle

Verma, S, Lovren, F, Dumont, AS, Mather, KJ, Maitland, A, Kieser, TM, Triggle, C & Anderson, TJ 2000, 'Tetrahydrobiopterin improves endothelial function in human saphenous veins', Journal of Thoracic and Cardiovascular Surgery, vol. 120, no. 4, pp. 668-671.
Verma S, Lovren F, Dumont AS, Mather KJ, Maitland A, Kieser TM et al. Tetrahydrobiopterin improves endothelial function in human saphenous veins. Journal of Thoracic and Cardiovascular Surgery. 2000;120(4):668-671.
Verma, Subodh ; Lovren, Fina ; Dumont, Aaron S. ; Mather, Kieren J. ; Maitland, Andrew ; Kieser, Teresa M. ; Triggle, Christopher ; Anderson, Todd J. / Tetrahydrobiopterin improves endothelial function in human saphenous veins. In: Journal of Thoracic and Cardiovascular Surgery. 2000 ; Vol. 120, No. 4. pp. 668-671.
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abstract = "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 tetrahydro-biopterin 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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AU - Maitland, Andrew

AU - Kieser, Teresa M.

AU - Triggle, Christopher

AU - Anderson, Todd J.

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