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Am J Physiol Heart Circ Physiol 281: H75-H83, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 1, H75-H83, July 2001

HMG-CoA reductase inhibitor stabilizes rabbit atheroma by increasing basal NO and decreasing superoxide

Navin Kumar Thakur, Toshio Hayashi, Daigo Sumi, Hatsuyo Kano, Taku Tsunekawa, and Akihisa Iguchi

Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan

Male rabbits fed a 0.5% cholesterol diet for 8 wk were divided into three groups. Group 1 was hypercholesterolemic; group 2 was fed a regular diet for an additional 12 wk; and group 3 was fed a regular diet with simvastatin (5 mg · kg-1 · day-1). Simvastatin treatment reduced the atherosclerotic area and total and esterified cholesterol concentrations in the thoracic aorta. Tone-related basal nitric oxide (NO) release was highest in group 3. Acetylcholine-induced, NO-dependent relaxation was improved in group 3 compared with group 2. Amount of endothelial nitric oxide synthase (eNOS) mRNA in vessels increased in group 1, compared with normal aorta, and decreased in group 2; however, it did not decrease in group 3. The amount of O<UP><SUB>2</SUB><SUP>−</SUP></UP> released from vessels increased in group 1 and group 2 compared with normal rabbits; however, it decreased in group 3, especially in the endothelial cells. Peroxynitrite determined by nitrotyrosine staining decreased in group 3. Additionally, the arteries of rabbits fed a regular diet with or without simvastatin were investigated. The aorta from simvastatin-treated group showed increase of tone-related basal NO release and eNOS mRNA and decrease of O<UP><SUB>2</SUB><SUP>−</SUP></UP> release. Taken together, upregulation of eNOS and decrease of O<UP><SUB>2</SUB><SUP>−</SUP></UP> treatment were observed in vivo in the process of the sufficient stabilization of atheroma following simvastatin.

atherosclerosis; stabilization; superoxide anion; nitric oxide synthase; hyperlipidemia


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