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

被引:40
作者
Dudgeon, S [1 ]
Benson, DP [1 ]
MacKenzie, A [1 ]
Paisley-Zyszkiewicz, K [1 ]
Martin, W [1 ]
机构
[1] Univ Glasgow, Clin Res Initiat, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
基金
英国惠康基金;
关键词
nitric oxide; endothelium; superoxide anion; superoxide dismutase; superoxide dismutase mimetic; oxidant stress; antioxidant; ascorbate;
D O I
10.1038/sj.bjp.0702120
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu M, reached a maximum of 45.3 +/- 2.8%, and was abolished by endothelial removal or treatment with L-NAME (100 mu M), 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 mu M) on endothelium-containing rings or adenosine (0.1 mu M - 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 < 0.001). Treatment with ascorbate (30 mu M - 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.
引用
收藏
页码:782 / 786
页数:5
相关论文
共 30 条
  • [1] VASCULAR BOUND RECOMBINANT EXTRACELLULAR SUPEROXIDE-DISMUTASE TYPE-C PROTECTS AGAINST THE DETRIMENTAL EFFECTS OF SUPEROXIDE RADICALS ON ENDOTHELIUM-DEPENDENT ARTERIAL RELAXATION
    ABRAHAMSSON, T
    BRANDT, U
    MARKLUND, SL
    SJOQVIST, PO
    [J]. CIRCULATION RESEARCH, 1992, 70 (02) : 264 - 271
  • [2] APPARENT HYDROXYL RADICAL PRODUCTION BY PEROXYNITRITE - IMPLICATIONS FOR ENDOTHELIAL INJURY FROM NITRIC-OXIDE AND SUPEROXIDE
    BECKMAN, JS
    BECKMAN, TW
    CHEN, J
    MARSHALL, PA
    FREEMAN, BA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (04) : 1620 - 1624
  • [3] Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production
    Bouloumie, A
    Bauersachs, J
    Linz, W
    Scholkens, BA
    Wiemer, G
    Fleming, I
    Busse, R
    [J]. HYPERTENSION, 1997, 30 (04) : 934 - 941
  • [4] COCCO D, 1981, J BIOL CHEM, V256, P8983
  • [5] Day BJ, 1995, J PHARMACOL EXP THER, V275, P1227
  • [6] RATES OF INTERACTIONS OF SUPEROXIDE WITH VITAMIN-E, VITAMIN-C AND RELATED-COMPOUNDS AS MEASURED BY CHEMILUMINESCENCE
    GOTOH, N
    NIKI, E
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1115 (03) : 201 - 207
  • [7] SUPEROXIDE ANION IS INVOLVED IN THE BREAKDOWN OF ENDOTHELIUM-DERIVED VASCULAR RELAXING FACTOR
    GRYGLEWSKI, RJ
    PALMER, RMJ
    MONCADA, S
    [J]. NATURE, 1986, 320 (6061) : 454 - 456
  • [8] Gutteridge J. M. C., 1989, FREE RADICALS BIOL M
  • [9] SUPEROXIDE-DISMUTASE RECOVERS ALTERED ENDOTHELIUM-DEPENDENT RELAXATION IN DIABETIC RAT AORTA
    HATTORI, Y
    KAWASAKI, H
    ABE, K
    KANNO, M
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 261 (04): : H1086 - H1094
  • [10] Hornig B, 1998, CIRCULATION, V97, P363