Contribution of Vascular NAD(P)H Oxidase to Endothelial Dysfunction in Heart Failure and the Therapeutic Effects of HMG-CoA Reductase Inhibitor
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概要
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Background The vascular NAD(P)H oxidase-derived superoxide anion (O_<2^->) plays a crucial role in the pathological progression of hypertension and atherosclerosis, and HMG-CoA reductase inhibitors (statins) have vascular antioxidant effects. However, it is unclear whether the vascular NAD(P)H oxidase is involved in the endothelial dysfunction of congestive heart failure (CHF) and whether HMG-CoA reductase inhibitors (statins) exert their vasoprotective effects in CHF. The present study examined both the involvement of vascular NAD(P)H oxidase in endothelial dysfunction in dogs with tachycardia-induced CHF and the therapeutic effect of a statin (pitavastatin). Methods and Results Femoral blood flow (FBF) responses to acetylcholine was significantly impaired in the CHF group, but were improved by pitavastatin. Vascular O_<2^-> production, NAD(P)H oxidase activity and Nox4 and p47phox expression were significantly elevated in CHF compared with the normal group. The elevated O_<2^-> production in the CHF group was suppressed by the NAD(P)H oxidase inhibitor, apocynin, to the normal level. In contrast, neither the gene expression nor the activity of endothelial nitric oxide synthase (eNOS) differed significantly between the normal and CHF groups. However, pitavastatin significantly suppressed O_<2^-> production, NAD(P)H oxidase activity and Nox4 and p47phox expression and increased eNOS expression and activity compared with the CHF group. Conclusions The activated vascular NAD(P)H oxidase contributes to endothelial dysfunction in CHF, which was partly improved by pitavastatin via its inhibition of NAD(P)H oxidase.
- 社団法人日本循環器学会の論文
- 2004-10-20
著者
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OHNISHI Masato
Department of Molecular and Functional Genomics, Center for Integrated Research in Science, Shimane
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TSUTAMOTO Takayoshi
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
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FUJII Masanori
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
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HORIE Minoru
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science
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Fujii Masanori
Department Of Cardiovascular And Respiratory Medicine Shiga University Of Medical Science
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Oonishi Masato
Cardiovascular And Heart Failure Center Kusatsu General Hospital
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ISONO Takahiro
Central Research Laboratory, Shiga University of Medical Science
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Wada Atsuyuki
Cardiovascular and Heart Failure Center, Kusatsu General Hospital
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Takayama Tomoyuki
Division of cardiology, Koga Hospital
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Takayama Tomoyuki
Department of Cardiovascular Medicine, Shiga University of Medical Science
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Wada Atsuyuki
Department of Cardiovascular and Respiratory Medicine, Shiga-University of Medical Science
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Wada Atsuyuki
Cardiovascular And Heart Failure Center Kusatsu General Hospital
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Tsutamoto Takayoshi
Department Of Cardiovascular And Respiratory Medicine
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Horie Minoru
Department Of Cardiac Physiology National Cardiovascular Center Research Institute
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Isono Takahiro
Central Research Laboratory Shiga University Of Medical Science
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Ohnishi Masato
Department Of Cardiovascular And Respiratory Medicine Shiga University Of Medical Science
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