Tetrahydrobiopterin Improves Endothelial Function in Patients with Coronary Artery Disease
Abstract
Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS) and a scavenger of oxygen-derived free radicals. Decreased availability of BH4 leads, under in vitro conditions, to reduced nitric oxide (NO) production and increased superoxide formation. We studied the effect of exogenous BH4 on endothelial function of angiographically normal vessel segments in patients with coronary artery disease. Nineteen patients with coronary artery disease underwent quantitative coronary angiography with simultaneous coronary flow velocity measurements (Cardiometrics FloWire). Data were obtained in angiographically normal segments of the left coronary artery at baseline, after intracoronary (i.c.) administration of acetylcholine (Ach; 10(-4) M), after infusion of BH4 (10(-2) M), and after co-infusion of ACh and BH4. At the end of the study, 300 microg nitroglycerin (NTG) i.c. was administered to obtain maximal vasodilation. At each step, flow velocity was determined before and after 18 microg adenosine i.c. to assess coronary flow velocity reserve. In 15 patients, ACh induced coronary vasoconstriction of -18 +/- 3% (endothelial dysfunction; p < 0.0001 vs. baseline), and in four patients, vasodilation of +39 +/- 20%. In the 15 patients with endothelial dysfunction, BH4 alone did not influence vessel area but prevented vasoconstriction to ACh (+2 +/- 3%, NS, vs. baseline). Correspondingly, calculated volume flow showed the highest value after co-infusion of ACh and BH4. Coronary flow velocity reserve was comparable during the various infusion steps. BH4 prevents ACh-induced vasoconstriction of angiographically normal vessels in patients with coronary artery disease. Thus substitution of this cofactor of NOS may represent a new approach for the treatment of endothelial dysfunction.
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AO reduces nitrite to NO, albeit at a slower rate than XO.
“AO has been shown to reduce nitrite to NO, albeit a slower rate than XO (Table 4) (568, 575, 617, 1001).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [617]
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- Authors
- Maier, W., Cosentino, F., Lütolf, R. B., Fleisch, M., Seiler, C., Hess, O. M., Meier, B., & Lüscher, T. F.
- Affiliations
- University Hospital of Bern (CH)
- Corresponding author
- Lüscher, Thomas F.
- Venue
- Journal of Cardiovascular Pharmacology
- Published
- 2000-02
- Volume
- 35
- Issue
- 2
- Pages
- 173-178
- ISSN
- 0160-2446 (ISSN-L)
- OpenAlex
- W2011089437
- Cited by
- 217
- References
- 24
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 5 · 2012: 11
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cardiovascular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Keywords
- tetrahydrobiopterin, endothelial dysfunction, coronary artery disease, nitric oxide synthase cofactor, acetylcholine-induced vasoconstriction, coronary flow velocity, coronary flow velocity reserve, nitric oxide, superoxide, nitroglycerin, adenosine
- MeSH terms
- Acetylcholine, Adenosine, Aged, Angiography, Antioxidants, Biopterins, Coronary Disease, Coronary Vessels, Drug Interactions, Endothelium, Vascular, Female, Nitroglycerin, Humans, Male, Middle Aged, Vasoconstriction, Vasodilator Agents
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