HMG-CoA reductase inhibitor stabilizes rabbit atheroma by increasing basal NO and decreasing superoxide.
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 x kg(-1) x 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 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 release. Taken together, upregulation of eNOS and decrease of O treatment were observed in vivo in the process of the sufficient stabilization of atheroma following simvastatin.
Thakur
N K
NK
Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Hayashi
T
T
Sumi
D
D
Kano
H
H
Tsunekawa
T
T
Iguchi
A
A
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology*; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D013481:Superoxides; D009569:Nitric Oxide; D002784:Cholesterol; D019821:Simvastatin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III