Cited by 400Nitric Oxide and Endothelin EffectsAntioxidant Activity and Oxidative StressRedox biology and oxidative stress

Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations

Jackson, Terence S., Xu, Aiming, Vita, Joseph A., Keaney, John F.·1998·Circulation Research

Abstract

The bioactivity of nitric oxide (.NO) depends, in part, on its interaction with superoxide. Usually, superoxide dismutase (SOD) preserves .NO bioactivity by limiting the availability of superoxide. Ascorbic acid also effectively scavenges superoxide, but the extent to which this interaction is necessary for intact .NO bioactivity is not known. Therefore, the present study examined the effect of ascorbic acid on .NO bioactivity with isolated rabbit arterial segments. A steady flux of superoxide (1.15 to 2.3 micromol . L-1 . min-1) produced either by pyrogallol autoxidation or a hypoxanthine/xanthine oxidase system inhibited endothelium-derived .NO-mediated arterial relaxation elicited by acetylcholine. This effect of superoxide was completely blocked by SOD (300 IU/mL) and the manganese SOD mimic EUK-8 (300 micromol/L) and partially inhibited by ascorbic acid (10 mmol/L). Lower concentrations of ascorbic acid were ineffective despite scavenging >90% of superoxide. We increased the endogenous flux of superoxide (3.2+/-0.3-fold) by inhibiting vascular copper-zinc SOD with diethyldithiocarbamate. This increased endogenous flux of superoxide produced an impairment of .NO-mediated arterial relaxation that was reversed by EUK-8 (300 micromol/L) but not ascorbic acid (10 mmol/L) despite equivalent scavenging of the endogenous superoxide flux. We used 3-nitrotyrosine formation (from peroxynitrite) as an indicator of .NO interaction with superoxide and found that SOD and EUK-8 compete more effectively with .NO for superoxide than does ascorbic acid. These data indicate that preservation of .NO bioactivity by superoxide scavengers depends not only on superoxide scavenging activity, but also on the rate of superoxide scavenging. Normal extracellular concentrations of ascorbic acid (30 to 150 micromol/L) are not likely to prevent the interaction of .NO with superoxide under physiological conditions.

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  • In competition with NO, a concentration of vitamin C about 10 mM is needed to block the interaction of NO with the superoxide by effective scavenging of the latter.

    “However, in competition with NO, a concentration of vitamin C about 10 mM is needed to block the interaction of NO with the superoxide by effective scavenging of the latter [167].”

    From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [167]

    The Discussion says 10 mmol/L ascorbic acid was required to achieve any effect in the experimental system, supporting the need for a high concentration. But the section “Ascorbic Acid and Superoxide Competition for NO” says it was only partially effective even at 10 mmol/L, so the source does not support saying that concentration blocks the interaction. Page numbers were not supplied. (LLM, conf=0.88)

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Authors
Jackson, T. S., Xu, A., Vita, J. A., & Keaney, J. F.
Affiliations
Boston University (US)
Venue
Circulation Research
Published
1998-11-02
Volume
83
Issue
9
Pages
916-922
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
OpenAlex
W2155603952
Cited by
400
References
48
Citations by year
2025: 9 · 2024: 6 · 2023: 4 · 2022: 4 · 2021: 18 · 2020: 15 · 2019: 13 · 2018: 9 · 2017: 7 · 2016: 14 · 2015: 12 · 2014: 17 · 2013: 17 · 2012: 21
FWCI
11.04
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association
  • National Institutes of Health (5r01hl059346-02, HL59346, HL55854, 1r01hl053398-01a1)
  • National Heart, Lung, and Blood Institute (HL59346, HL 53398, P01HL055854, HL-55854)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
vitamin C, superoxide, nitric oxide, superoxide dismutase, peroxynitrite, nitrotyrosine, endothelium-derived nitric oxide, acetylcholine-induced relaxation, diethyldithiocarbamate
MeSH terms
Animals, Ascorbic Acid, Endothelium, Vascular, Female, Male, Nitric Oxide, Pyrogallol, Rabbits, Superoxides, Vasodilation

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