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Recent evidence suggests that dietary therapy with lipid-soluble antioxidants may be beneficial for patients with atherosclerotic vascular disease but the potential mechanism(s) for these observations remain obscure. Abnormalities in endothelium-dependent control of vascular tone develop early in the course of atherosclerosis and may result from oxidative modification of low density lipoproteins. We examined the role of dietary antioxidants in preserving normal endothelial cell vasodilator function in cholesterol-fed rabbits with particular attention to possible effects on serum lipoproteins, low density lipoprotein oxidation, and atherogenesis. Male New Zealand White rabbits were fed diets containing no additive (controls), 1% cholesterol (cholesterol group), or 1% cholesterol chow supplemented with either beta-carotene (0.6 g/kg of chow) or alpha-tocopherol (1000 international units/kg of chow) for a 28-day period. After dietary therapy, thoracic aortae were harvested for assay of vascular function and for pathologic examination and tissue antioxidant levels. Compared to controls, acetylcholine- and A23187-mediated endothelium-dependent relaxations were significantly impaired in vessels from the cholesterol group (P < 0.001), whereas vessels from animals treated with beta-carotene or alpha-tocopherol demonstrated normal endothelium-dependent arterial relaxation. Preservation of endothelial function was associated with vascular incorporation of alpha-tocopherol and beta-carotene but was unrelated to plasma lipoprotein levels, smooth muscle cell function, or the extent of atherosclerosis. Increased low density lipoprotein resistance to ex vivo copper-mediated oxidation was observed only in the alpha-tocopherol group. Our results suggest that dietary antioxidants may benefit patients with atherosclerosis by preserving endothelial vasodilator function through a mechanism related to vascular tissue antioxidant content and not reflected by assay of low density lipoprotein resistance to ex vivo oxidation.
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J F Keaney, and
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J Curran-Celentano, and
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March 1989,
The American journal of physiology,
J F Keaney, and
J M Gaziano, and
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J Curran-Celentano, and
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December 1990,
Circulation research,
J F Keaney, and
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January 2006,
Chang Gung medical journal,
J F Keaney, and
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May 1993,
Atherosclerosis,
J F Keaney, and
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April 1991,
Cardiovascular research,
J F Keaney, and
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G T Shwaery, and
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December 1990,
Deutsche medizinische Wochenschrift (1946),
J F Keaney, and
J M Gaziano, and
A Xu, and
B Frei, and
J Curran-Celentano, and
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J A Vita
April 1998,
The American journal of the medical sciences,
J F Keaney, and
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A Xu, and
B Frei, and
J Curran-Celentano, and
G T Shwaery, and
J Loscalzo, and
J A Vita
September 1994,
Cardiovascular research,
J F Keaney, and
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A Xu, and
B Frei, and
J Curran-Celentano, and
G T Shwaery, and
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August 1994,
Alcoholism, clinical and experimental research,
