Recovery by ascorbate of impaired nitric oxide‐dependent relaxation resulting from oxidant stress in rat aorta

1 In this study we investigated the ability of ascorbate to protect nitric oxide from destruction by superoxide anion. 2 Ascorbate produced concentration‐dependent relaxation of rings of rat aorta, comprising two components: the first, seen at 1–300 μM, reached a maximum of 45.3±2.8%, and was abolis...

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Bibliographic Details
Published in:British journal of pharmacology 1998-10, Vol.125 (4), p.782-786
Main Authors: Dudgeon, Sinead, Benson, David P, MacKenzie, Andrew, Paisley‐Zyszkiewicz, Karen, Martin, William
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Animals
antioxidant
Aorta - drug effects
ascorbate
Ascorbic Acid - metabolism
Ascorbic Acid - pharmacology
Biological and medical sciences
Cardiovascular system
Dose-Response Relationship, Drug
Drug Interactions
endothelium
Endothelium, Vascular - physiology
Female
Medical sciences
Miscellaneous
Muscle Relaxation - drug effects
Muscle, Smooth - drug effects
Nitric oxide
Nitric Oxide - pharmacology
oxidant stress
Oxidative Stress - physiology
Pharmacology. Drug treatments
Rats
Rats, Wistar
superoxide anion
superoxide dismutase
Superoxide Dismutase - drug effects
superoxide dismutase mimetic
Superoxides - pharmacology
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Summary:1 In this study we investigated the ability of ascorbate to protect nitric oxide from destruction by superoxide anion. 2 Ascorbate produced concentration‐dependent relaxation of rings of rat aorta, comprising two components: the first, seen at 1–300 μM, reached a maximum of 45.3±2.8%, and was abolished by endothelial removal or treatment with L‐NAME (100 μM), demonstrating involvement of nitric oxide. The second occurred at concentrations of 1 mM and above and was associated with falls in the pH of the bathing fluid. 3 Pretreatment with ascorbate at concentrations up to 3 mM had no effect on the relaxation to acetylcholine (10 nM–10 μM) on endothelium‐containing rings or adenosine (0.1 μM–3 mM) on endothelium‐denuded rings. 4 An oxidant stress was applied to aortic rings, comprising inhibition of endogenous Cu/Zn superoxide dismutase by diethyldithiocarbamate (0.1 mM) followed by generation of superoxide anion by hypoxanthine (0.1 mM/xanthine oxidase (16 u ml−1). This reduced maximal acetylcholine‐induced relaxation from 96.7±1.3% to 42.4±3.5% (P
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0702120