The DOI matches its Crossref record; 119 of the 119 references it cites were found in a registry or an index.
How does ascorbic acid prevent endothelial dysfunction?
Abstract
Human coronary and peripheral arteries show endothelial dysfunction in a variety of conditions, including atherosclerosis, hypercholesterolemia, smoking, and hypertension. This dysfunction manifests as a loss of endothelium-dependent vasodilation to acetylcholine infusion or sheer stress, and is typically associated with decreased generation of nitric oxide (NO) by the endothelium. Vitamin C, or ascorbic acid, when acutely infused or chronically ingested, improves the defective endothelium-dependent vasodilation present in these clinical conditions. The mechanism of the ascorbic acid effect is unknown, although it has been attributed to an antioxidant function of the vitamin to enhance the synthesis or prevent the breakdown of NO. In this review, multiple mechanisms are considered that might account for the ability of ascorbate to preserve NO. These include ascorbate-induced decreases in low-density lipoprotein (LDL) oxidation, scavenging of intracellular superoxide, release of NO from circulating or tissue S-nitrosothiols, direct reduction of nitrite to NO, and activation of either endothelial NO synthase or smooth muscle guanylate cyclase. The ability of ascorbic acid supplements to enhance defective endothelial function in human diseases provides a rationale for use of such supplements in these conditions. However, it is first necessary to determine which of the many plausible mechanisms account for the effect, and to ensure that undesirable toxic effects are not present.
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“Ascorbate also supports NO signalling by maintaining an intracellular redox balance, promoting the formation of S-nitrosothiols (RSNOs) as NO reservoirs, and facilitating nitrite reduction under acidic conditions [61,63].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [63]
In the citing paper
“Vitamins C and E reduce superoxide accumulation and lipid peroxidation, thereby preserving endothelial function.”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [63]
Citations
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Role of Oxidative Modifications in Atherosclerosis
Stocker, R., & Keaney, J. F. (2004) · Physiological Reviews · doi:10.1152/physrev.00047.2003 · Cited by 2,651
Halliwell, B., & Whiteman, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705776 · Cited by 2,238
Kohen, R., & Nyska, A. (2002) · Toxicologic Pathology · doi:10.1080/01926230290166724 · Cited by 2,178
Dietary factors and low-grade inflammation in relation to overweight and obesity
Calder, P. C., Ahluwalia, N., Brouns, F., Buetler, T., Clement, K., Cunningham, K., Esposito, K., Jönsson, L. S., Kolb, H., Lansink, M., et al. (2011) · British Journal of Nutrition · doi:10.1017/s0007114511005460 · Cited by 1,098
Vitamins C and E: Beneficial effects from a mechanistic perspective
Traber, M. G., & Stevens, J. F. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.017 · Cited by 1,076
Metadata
- Authors
- May, J. M.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- May, James M
- ORCID
- May, James M
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2000-05
- Volume
- 28
- Issue
- 9
- Pages
- 1421-1429
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2074030075
- Cited by
- 260
- References
- 119
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 7 · 2022: 8 · 2021: 10 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 5 · 2016: 9 · 2015: 13 · 2014: 8 · 2013: 11 · 2012: 12
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK050435, DK-50435)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- vitamin C, endothelial dysfunction, nitric oxide, endothelium-dependent vasodilation, antioxidant defense, LDL oxidation, superoxide radical scavenging, S-nitrosothiols, nitrite reduction, endothelial nitric oxide synthase, guanylate cyclase, atherosclerosis, hypercholesterolemia, hypertension, smoking
- MeSH terms
- Animals, Antioxidants, Arteriosclerosis, Ascorbic Acid, Coronary Vessels, Endothelium, Vascular, Enzyme Activation, Guanylate Cyclase, Humans, Lipoproteins, LDL, Mercaptoethanol, Nitric Oxide, Nitrites, Nitroso Compounds, Oxidation-Reduction, Rabbits, Sulfhydryl Compounds, Superoxides, Vasodilation, Oxidative Stress, Nitric Oxide Synthase, S-Nitrosothiols, Nitric Oxide Synthase Type III
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