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 microM, reached a maximum of 45.3+/-2.8%, and was abolished by endothelial removal or treatment with L-NAME (100 microM), 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 microM) on endothelium-containing rings or adenosine (0.1 microM-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 microM-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.
Dudgeon
S
S
Clinical Research Initiative, Institute of Biomedical & Life Sciences, University of Glasgow.
Benson
D P
DP
MacKenzie
A
A
Paisley-Zyszkiewicz
K
K
Martin
W
W
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000187:drug effects; D013481:Superoxides / Q000494:pharmacology*
D013481:Superoxides; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D000109:Acetylcholine; D001205:Ascorbic Acid