Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant Rats
スポンサーリンク
概要
- 論文の詳細を見る
Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O2−) generation in the insulin-resistant state. We investigated the effects of atorvastatin, a 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor; amlodipine, a calcium antagonist; and their combination on blood pressure, arterial relaxation and contraction, and vascular oxidative stress in aortas of high fructose–fed rats. Oral administration of atorvastatin for 8 weeks did not significantly lower blood pressure, but normalized angiotensin II–induced vasoconstriction and endothelial function in the fructose-fed rats. Atorvastatin treatment of fructose-fed rats increased vascular BH4 content, which was associated with an increase in endothelial NO synthase activity as well as a reduction in endothelial O2− production. On the other hand, administration of amlodipine did not affect the angiotensin II–induced vasoconstriction and endothelial function, but normalized the elevated blood pressure in the fructose-fed rats. The combined treatment did not show synergistic but additive beneficial effects. The present study suggests that combined therapy of HMG-CoA reductase inhibitors and calcium antagonists prevents functional vascular disorders in the insulin-resistant state, possibly resulting in the protection against or delay of development of hypertension, vascular dysfunction in diabetes, and thereafter atherosclerosis.
著者
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Shintaku Haruo
Department Of Pediatrics Osaka City University
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Okamura Tomio
Department Of Pharmacology
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Masada Masahiro
Laboratory Of Biochemistry Faculty Of Horticulture Chiba University
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Shinozaki Kazuya
Department Of Pharmacology
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Imamura Takeshi
Department Of Applied Physics Faculty Of Science Tokyo Institute Of Technology:(present Address) Fuj
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Geddawy Ayman
Department Of Pharmacology Shiga University Of Medical Science
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Tawa Masashi
Department Of Pharmacology Shiga University Of Medical Science
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Shimosato Takashi
Department Of Pharmacology Shiga University Of Medical Science
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Shimosato Takashi
Department of Pharmacology, Shiga University of Medical Science, Japan
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Yoshida Yuichi
Laboratory of Biochemistry, Faculty of Horticulture, Chiba University, Japan
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Masada Masahiro
Laboratory of Biochemistry, Faculty of Horticulture, Chiba University, Japan
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Geddawy Ayman
Department of Pharmacology, Shiga University of Medical Science, Japan
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Iwasaki Hirotaka
Department of Pharmacology, Shiga University of Medical Science, Japan
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Shintaku Haruo
Department of Pediatrics, Osaka City University Graduate School of Medicine, Japan
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