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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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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
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description 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
doi_str_mv 10.1038/sj.bjp.0702120
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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&lt;0.001). Treatment with ascorbate (30 μM–3 mM) reversed this blockade in a concentration‐dependent manner. 5 Our findings show that ascorbate has the ability to protect nitric oxide from destruction by superoxide anion. This action is seen with ascorbate at levels normally present in plasma, suggesting that this antioxidant may exert a tonic protective effect on nitric oxide within the vasculature. 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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&lt;0.001). Treatment with ascorbate (30 μM–3 mM) reversed this blockade in a concentration‐dependent manner. 5 Our findings show that ascorbate has the ability to protect nitric oxide from destruction by superoxide anion. This action is seen with ascorbate at levels normally present in plasma, suggesting that this antioxidant may exert a tonic protective effect on nitric oxide within the vasculature. 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Drug treatments</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>superoxide anion</topic><topic>superoxide dismutase</topic><topic>Superoxide Dismutase - drug effects</topic><topic>superoxide dismutase mimetic</topic><topic>Superoxides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dudgeon, Sinead</creatorcontrib><creatorcontrib>Benson, David P</creatorcontrib><creatorcontrib>MacKenzie, Andrew</creatorcontrib><creatorcontrib>Paisley‐Zyszkiewicz, Karen</creatorcontrib><creatorcontrib>Martin, William</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dudgeon, Sinead</au><au>Benson, David P</au><au>MacKenzie, Andrew</au><au>Paisley‐Zyszkiewicz, Karen</au><au>Martin, William</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recovery by ascorbate of impaired nitric oxide‐dependent relaxation resulting from oxidant stress in rat aorta</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>1998-10</date><risdate>1998</risdate><volume>125</volume><issue>4</issue><spage>782</spage><epage>786</epage><pages>782-786</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>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&lt;0.001). Treatment with ascorbate (30 μM–3 mM) reversed this blockade in a concentration‐dependent manner. 5 Our findings show that ascorbate has the ability to protect nitric oxide from destruction by superoxide anion. This action is seen with ascorbate at levels normally present in plasma, suggesting that this antioxidant may exert a tonic protective effect on nitric oxide within the vasculature. British Journal of Pharmacology (1998) 125, 782–786; doi:10.1038/sj.bjp.0702120</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>9831915</pmid><doi>10.1038/sj.bjp.0702120</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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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
title Recovery by ascorbate of impaired nitric oxide‐dependent relaxation resulting from oxidant stress in rat aorta
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