Adenosine-Induced Dilation of Coronary Resistance Vessels Is Impaired in Rats with Type 2 Diabetes Mellitus: Possible Role of ATP-Sensitive Potassium Channels and Nitric Oxide
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概要
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Objectives The purpose of this study was to test the hypothesis that adenosine-induced coronarymicrovascular dilation is blunted in the animals with diabetes mellitus（ DM） through the impairment of KATP channelfunction. Background Adenosine-induced coronary vasodilation is demonstrated to be mediated by activation of ATPsensitivepotassium（ KATP） channels and nitric oxide（ NO）. Methods The hearts of Otsuka Long-Evans Tokushima fatty rats （OLETF, type 2 DM rats）, and control Long-Evans Tokushima fatty rats（ LETO） at the ages of 32 and 8 weeks were perfused using a Langendorff system withconstant perfusion pressure （80 mmHg）. Changes in coronary fl ow to adenosine, pinacidil and sodium nitroprusside（SNP） were examined before and after administration of glibenclamide（ 10-7 M）, or NG-nitro-L-arginine methyl ester（L-NAME, 10-4 M）. Results At the age of 32 weeks, adenosine- and pinacidil-induced increases in coronary fl ow were blunted in OLETFas compared with those in LETO （both p<0.05）. Glibenclamide attenuated adenosine-induced increase in coronaryfl ow in LETO （p<0.05）, but not in OLETF. In contrast, L-NAME attenuated adenosine-induced increase in coronaryflow in OLETF （p<0.05）, but not in LETO. SNP-induced increases in coronary flow in LETO and OLETF werecomparable and were not aff ected by glibenclamide. In 8-week-old OLETF and LETO, no diff erence was observed inadenosine-, pinacidil- and SNP-induced increases in coronary fl ow between OLETF and LETO. Conclusions In this type 2 DM model, KATP channel function in coronary microcirculation is impaired. Adenosineinducedincrease in coronary fl ow is mediated mainly by NO mechanism.
著者
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Hasegawa Kazushi
Department of Cardiology Respiratory Medicine and Nephrology, Hirosaki University Graduate School of
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Yoshida Ikko
Department of Cardiology Respiratory Medicine and Nephrology, Hirosaki University Graduate School of
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Ishizaka Hiroshi
Department of Cardiology Respiratory Medicine and Nephrology, Hirosaki University Graduate School of
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Osanai Tomohiro
Department of Cardiology Respiratory Medicine and Nephrology, Hirosaki University Graduate School of
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Motomura Shigeru
Department of Pharmacology, Hirosaki University Graduate School of Medicine
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Okumura Ken
Department of Cardiology Respiratory Medicine and Nephrology, Hirosaki University Graduate School of
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Okumura Ken
心臓血管研究所
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Okumura Ken
Department Of Cardiology Respiratory Medicine And Nephrology Hirosaki University Graduate School Of
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Okumura Ken
Department Of Cardiology Hirosaki University Graduate School Of Medicine
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Okumura Ken
Kumamoto University School Of Medicine Kumamoto Japan
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Yoshida Ikkou
Department Of Cardiology Respiratory Medicine And Nephrology Hirosaki University Graduate School Of
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Okumura Ken
The First Department Of Internal Medicine Kumamoto University Medical School
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Satoh Kiyohiko
Department of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School o
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Okumura Ken
Department Of Cardiology Hirosaki University Graduate School Of Medicine Hirosaki Japan
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Motomura Shigeru
Department Of Pharmacology Hirosaki University Graduate School Of Medicine
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Motomura Shigeru
Department Of Pharmacology Hirosaki University
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Hasegawa Kazushi
Department Of Cardiology Respiratory Medicine And Nephrology Hirosaki University Graduate School Of
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Okumura Ken
Department Of Cardiology Hirosaki University School Of Medicine
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Osanai Tomohiro
Department Of Cardiology Hirosaki University Graduate School Of Medicine Hirosaki Japan
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Satoh Kiyohiko
Department Of Cardiology Respiratory Medicine And Nephrology Hirosaki University Graduate School Of
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Osanai Tomohiro
Department Of Cardiology Hirosaki University Graduate School Of Medicine
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Osanai Tomohiro
Department Of Cardiology Hirosaki University School Of Medicine
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Ishizaka Hiroshi
Department Of Cardiology Respiratory Medicine And Nephrology Hirosaki University Graduate School Of
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Ishizaka Hiroshi
The Second Department Of Internal Medicine Hirosaki University School Of Medicine
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Hasegawa Kazushi
Department Of Cardiology Hirosaki University Graduate School Of Medicine Hirosaki Japan
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Okumura Ken
The Division Of Cardiology Hirosaki University Graduate School Of Medicine
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Okumura Ken
Department Of Cardiology Hirosaki University Hospital
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Hasegawa Kazushi
Department Of Cardiology Hirosaki University Graduate School Of Medicine
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Inokubo Yoichi
Department Of Cardiology Hachinohe City Hospital
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吉田 一弘
Department of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine
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石坂 浩
Department of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine
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長谷川 一志
Department of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine
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Motomura Shigeru
Department of Pharmacalogy, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine
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Okumura Ken
Department of Advance Management of Cardiac Arrhythmias Hirosaki University Graduate School of Medicine
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