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Journal of Cardiovascular Pharmacology and Therapeutics
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Relative Effects of {alpha}- and {gamma}-Tocopherol on Low-Density Lipoprotein Oxidation and Superoxide Dismutase and Nitric Oxide Synthase Activity and Protein Expression in Rats

Dayuan Li

Department of Medicine, University of Florida, and VA Medical Center, Gainesville, Florida

Tom Saldeen

Department of Forensic Medicine, University of Uppsala, Uppsala, Sweden

Francesco Romeo

Department of Cardiology, University of Catania, Italy

Jawahar L. Mehta

Department of Medicine, University of Florida, and VA Medical Center, Gainesville, Florida

Background: Increasing evidence suggests that vitamin E prevents the progression of ath erosclerosis by inhibiting platelet aggregation, monocyte adhesion. and improving plaque stability and vasomotor function. Recently, controversy has arisen as to the relative effects of {alpha}- and {gamma}-tocopherol in modulating some mediators of atherosclerosis.

Methods and Results: We examined the effects of {alpha}- and {gamma}-tocopherol on constitutive nitric oxide synthase (cNOS) and superoxide dismutase (SOD) activity and protein expression in rats. Sprague-Dawley rats were fed regular chow or chow mixed with {alpha}- or {gamma}-tocopherol (100 mg/kg/ day) for 7 to 10 days. Plasma {alpha}- and {gamma}-tocopherol levels, low-density lipoprotein (LDL) oxida tion, and cNOS and SOD activity and protein expression were measured. Plasma {alpha}-tocopherol levels were significantly increased (P < .01 vs control), but {gamma}-tocopherol levels fell (P < .01 vs control) in rats fed {alpha}-tocopherol. Plasma {gamma}-tocopherol levels were increased (P < .01 vs con trol), and {alpha}-tocopherol levels did not change in rats fed {gamma}-tocopherol. Both {alpha}- and {gamma}-tocopherol feeding decreased the rate of LDL oxidation induced by phorbol 12-myristate 13-acetate (PMA)-stimulated leukocytes (P < .01 vs control). Both {alpha}- and {gamma}-tocopherol increased SOD activity in plasma and arterial tissues as well as Mn SOD and Cu/Zn SOD protein expression in arterial tissues (all P < .01 vs control). {gamma}-Tocopherol was more potent than {alpha}-tocopherol in all these effects (P < .05). Both a- and {gamma}-tocopherol increased NO generation and cNOS activity (all P < .05 vs control). However, only {gamma}-tocopherol increased cNOS protein expression.

Conclusions: These observations indicate that whereas both {alpha}- and {gamma}-tocopherol exert important effects on determinants of oxidation and vasomotor function, effects of dietary {alpha}-tocopherol supplementation in vivo are less pronounced than those of {gamma}-tocopherol supplementation.

Key Words: vitamin E • nitric oxide synthase • superoxide dismutase.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 4, No. 4, 219-226 (1999)
DOI: 10.1177/107424849900400403


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