Effect of Vitamin C on the Availability of Tetrahydrobiopterin in Human Endothelial Cells
Abstract
Vitamin C has long been known for its beneficial vascular effects, but its mechanism of action remains unclear. Recent reports suggest that vitamin C may prevent endothelial dysfunction by scavenging free radicals and increasing the bioavailability of nitric oxide. To investigate this area further, we studied the effect of vitamin C (10(-4) M) and Mn(III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP; 10(-5) M), a scavenger of superoxide, hydrogen peroxide, and peroxynitrite, on endothelial nitric oxide synthase (eNOS) enzymatic activity in cultured human umbilical vein endothelial cells. L-Citrulline formation (a measure of eNOS enzymatic activity) was significantly increased in cells treated for 24 h with vitamin C. No effect was observed after MnTBAP treatment. Chronic administration of vitamin C also had no effect on eNOS protein expression. Treatment with vitamin C for 24 h significantly increased levels of the eNOS co-factor tetrahydrobiopterin (BH4), whereas MnTBAP did not affect its levels. Sepiapterin (10(-4) M), a precursor of BH4, significantly increased eNOS activity, whereas addition of vitamin C to cells treated with sepiapterin did not cause any further increase in eNOS activity. Our results suggest that the beneficial effect of vitamin C on endothelial function is best explained by increased intracellular BH4 content and subsequent enhancement of eNOS activity. This effect appears to be independent of the ability of vitamin C to scavenge superoxide anions.
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Treatment with antioxidants improves endothelial function in certain conditions.
“As the treatment with antioxidants has been shown to improve endothelial function in certain conditions (56, 419, 420, 422, 572), it is possible that the coadministration of BH4 with ascorbic acid or other antioxidants can circumvent these issues.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [56]
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- Authors
- Baker, T. A., Milstien, S., & Katusic, Z. S.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Milstien, Sheldon
- Venue
- Journal of Cardiovascular Pharmacology
- Published
- 2001-03
- Volume
- 37
- Issue
- 3
- Pages
- 333-338
- ISSN
- 0160-2446 (ISSN-L)
- OpenAlex
- W2320793908
- Cited by
- 113
- References
- 29
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 3 · 2015: 1 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 6.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cardiovascular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns037491-03)
- National Heart, Lung, and Blood Institute (HL-53524, R01HL053524)
- National Institute of Neurological Disorders and Stroke (NS-37491)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- vitamin C, tetrahydrobiopterin, endothelial nitric oxide synthase, endothelial dysfunction, MnTBAP, sepiapterin, citrulline, superoxide radical scavenging, nitric oxide bioavailability, human umbilical vein endothelial cells, peroxynitrite
- MeSH terms
- Ascorbic Acid, Biopterins, Cells, Cultured, Endothelium, Vascular, GTP Cyclohydrolase, Humans, Metalloporphyrins, Immunoblotting, Nitric Oxide Synthase, Nitric Oxide Synthase Type III
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