651. Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis.
- Author
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Lamb DJ, Tickner ML, Hourani SM, and Ferns GA
- Subjects
- Animals, Aorta, Thoracic enzymology, Arteriosclerosis enzymology, Arteriosclerosis metabolism, Calcimycin pharmacology, Carotid Arteries drug effects, Cholesterol blood, Copper analysis, Ionophores pharmacology, Muscle, Smooth drug effects, Oxidative Stress drug effects, Rabbits, Tyrosine analogs & derivatives, Tyrosine analysis, Aorta, Thoracic metabolism, Arteriosclerosis diet therapy, Copper administration & dosage, Dietary Supplements, Nitric Oxide metabolism, Superoxide Dismutase metabolism
- Abstract
The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R(2) = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R(2) = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis.
- Published
- 2005
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