Combination Therapy With Olmesartan and Azelnidipine Improves EDHF-Mediated Responses in Diabetic Apolipoprotein E-Deficient Mice
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概要
- 論文の詳細を見る
Background: The endothelium modulates vascular tone by synthesizing and releasing several vasodilating factors, including vasodilator prostaglandins, nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). In the present study, we examined whether an angiotensin-receptor blocker, a calcium-channel blocker or their combination improved EDHF-mediated responses in diabetic apolipoprotein E-deficient (ApoE-/-) mice. Methods and Results: We used male C57BL/6N (control) and streptozocin-induced diabetic ApoE-/- mice. The diabetic ApoE-/- mice were administered oral vehicle (untreated), olmesartan (OLM, 30 mg·kg-1·day-1), azelnidipine (AZL, 10 mg·kg-1·day-1), their combination (OLM + AZL), or hydralazine (HYD 5 mg·kg-1·day-1) for 5 weeks. In the untreated group, systolic blood pressure was significantly higher and both EDHF-mediated relaxation and endothelium-dependent hyperpolarization were markedly reduced as compared with the control group. Although EDHF-mediated relaxation was not significantly improved in the HYD, OLM and AZL groups, it was significantly improved in the OLM + AZL group, as was also the case with phosphorylation of Akt and endothelial NO synthase (eNOS). In contrast, the endothelium-independent relaxation response to sodium nitroprusside or NS-1619 (a direct opener of KCa channels) was unaltered in any group. Conclusions: OLM + AZL may improve the severely impaired EDHF-mediated responses in diabetic ApoE-/- mice, in which activation of the endothelial Akt - eNOS pathway may be involved. (Circ J 2010; 74: 798-806)
- 2010-03-25
著者
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Takahashi Atsushi
Department Of Cardiovascular Medicine Wakayama Medical University
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下川 宏明
東北大学循環器内科学
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Shimokawa Hiroaki
Department of Cardiology, Tohoku University School of Medicine
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Asaka Takahisa
Cardiovascular Center Yokosuka Kyosai Hospital
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Akasaka Takashi
Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Sato Hitoshi
Sports Clinic Juntendo University Hospital
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Shimokawa Hiroaki
Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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TAKAKI Aya
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
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OHASHI Junko
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
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Ohashi Junko
Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Asahara Takayuki
先端医療振興財団先端医療センター 血管再生研究グループ
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Shimokawa H
Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Hosoya Maki
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
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Sawada Ayuko
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
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Hosoya Maki
Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Sawada Ayuko
Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Takaki Aya
Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Shimokawa Hiroaki
Department Of Cardiology Tohoku University School Of Medicine
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Shimokawa Hiroaki
Kyushu University Graduate School Of Medical Sciences
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Asahara Takayuki
Regenerative Medicne Tokai University School Of Medicine
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Takaki Aya
Cardiovascular Center Yokosuka Kyosai Hospital
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Shimokawa Hiroaki
Department Of Cardiovascular Medicine Kyushu University Graduate School Of Medical Science
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Suzuka Hiroshi
Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine
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Asahara Takayuki
Department Of Medicine St.elizabeth's Medical Center Tufts University School Of Medicine
-
Shimokawa Hiroaki
From Reseach Institute Of Angiocardiology And Cardiovascular Clinic Faculty Of Medicine Kyushu Unive
-
Tanaka Atsushi
Department Of Internal Medicine And Cardiology Graduate School Of Medicine Osaka City University Med
-
Takaki Aya
Department Of Cardiovascular Medicine Kyushu University Graduate School Of Medical Sciences
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