Inhibitory Effects of Amlodipine and Fluvastatin on the Deposition of Advanced Glycation End Products in Aortic Wall of Cholesterol and Fructose-Fed Rabbits(Pharmacology)
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概要
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Recent studies suggest that advanced glycation end products (AGEs) can promote the development of atherosclerotic lesions in a similar manner to oxidatively modified low density lipoproteins. As oxidative stress accelerates the formation of AGEs, antioxidant drugs may exert atheroprotective effects via suppression of AGE formation. Although amlodipine, a calcium channel blocker, and fluvastatin, a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, show antioxidant and atheroprotective effects, the relation of AGEs to their effects is unknown. We immunohistochemically investigated the inhibitory effects of chronic treatment with amlodipine (5mg/kg per day) or fluvastatin at a dose insufficient to reduce plasma cholesterol levels (2mg/kg per day) on the accumulation of AGEs in atherosclerotic aortas of rabbits fed 1% cholesterol diet and 10% fructose containing water. After eight weeks of treatment, AGEs, namely argpyrimidine, carboxymethyllysine and pyrraline, markedly accumulated with intimal thickening in cholesterol and fructose-fed control rabbits, while the drugs inhibited those changes other than the pyrraline deposition without plasma lipid-lowering effects. Enhanced lipid peroxidation was observed in plasma from cholesterol and fructose-fed rabbits only, and lipid peroxidation was not suppressed by the drugs. These results suggest that the atheroprotective effects of the drugs are at least partly due to the suppression of AGE accumulation although the exact mechanism of AGE suppression is ambiguous.
- 公益社団法人日本薬学会の論文
- 2006-01-01
著者
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Oikawa Shinichi
Nippon Medical School
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AKIRA Kazuki
School of Pharmacy, Tokyo University of Pharmacy and Life Science
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AMANO Masayasu
School of Pharmacy, Tokyo University of Pharmacy and Life Science
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OKAJIMA Fuminobu
Nippon Medical School
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HASHIMOTO Takao
School of Pharmacy, Tokyo University of Pharmacy and Life Science
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Akira Kazuki
School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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Amano Masayasu
School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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Hashimoto Takao
School Of Pharmacy Tokyo University Of Pharmacy And Life Science
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