Cited by 260Nitric Oxide and Endothelin EffectsVitamin C and Antioxidants ResearchCardiovascular Health and Disease Prevention

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How does ascorbic acid prevent endothelial dysfunction?

May, James M·2000·Free Radical Biology and Medicine

DOI 10.1016/s0891-5849(00)00269-0

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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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See all 260

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)
DOI: 10.1016/s0891-5849(00)00269-0
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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