Malfunction of Vascular Control in Lifestyle-Related Diseases : Mechanisms Underlying Endothelial Dysfunction in the Insulin-Resistant State
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概要
- 論文の詳細を見る
It is tempting to speculate that increased vasoconstriction and loss of endothelium-dependent vasodilation might be etiological factors of elevated blood pressure in the insulin-resistant state. Vascular contraction induced by angiotensin II and the expression of NAD(P)H oxidase were increased in the aorta of insulin-resistant mice. In addition, both angiotensin II type 1 receptor expression and superoxide anion production were up-regulated in these mice. Another mechanism for imparing endothelial function is the uncoupling of endothelial nitric oxide synthase (eNOS). It has become clear from studies on the aorta of insulin-resistant rat that insulin resistance may be a pathogenic factor for endothelial dysfunction through impaired eNOS activity and increased oxidative breakdown of NO (nitric oxide) due to an enhanced formation of superoxide anion (NO/superoxide anion imbalance), which are caused by relative deficiency of tetrahydrobiopterin, a cofactor of NOS, in vascular endothelial cells. Supplementation of tetrahydrobiopterin restored endothelial function and relieved oxidative tissue damage through activation of eNOS in those rats. These results indicate that generation of superoxide anion from NAD(P)H oxidases and an uncoupled eNOS may be pathogenic factors for impaired endothelial function and hypertension in the insulin-resistant state.
- 社団法人 日本薬理学会の論文
- 2004-12-01
著者
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Kashiwagi Atsunori
Department Of Medicine Shiga University Of Medical Science
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Kashiwagi Atsunori
Third Department Of Medicine Shiga University Of Medical Science
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OKAMURA Tomio
Department of Pharmacology, Shiga University of Medical Science
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Okamura T
Department Of Pharmacology Shiga University Of Medical Science
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SHINOZAKI Kazuya
Department of Pharmacology, Shiga University of Medical Science
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AYAJIKI Kazuhide
Department of Pharmacology, Shiga University of Medical Science
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MASADA Masahiro
Laboratory of Biochemistry, Faculty of Horticulture, Chiba University
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Okamura Tomio
Department Of Pharmacology
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Okamura T
Shiga Univ. Medical Sci. Ohtsu Jpn
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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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Ayajiki Kazuhide
Department Of Pharmacology Shiga University Of Medical Science
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Ayajiki Kazuhide
Department Of Pharmacy School Of Pharmacy Hyogo University Of Health Sciences
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KASHIWAGI Atsunori
Department of Internal Medicine, Shiga University of Medical Science, Otsu
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Kashiwagi Atsunori
Department of Internal Medicine, Shiga University of Medical Science
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