| Project/Area Number |
09670713
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
MURAKAMI Tomoyuki Kyoto University, Postgraduate school of medicene, Lecturer, 医学研究科, 講師 (00190885)
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| Co-Investigator(Kenkyū-buntansha) |
HORIE Minoru Kyoto University, Postgraduate school of medicene, Assistant professor, 医学研究科, 助手 (90183938)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Myocardial Ischemia / K_<ATP> Channel / Angiotensin II / K_<ATP>チャネル / KATP channel / myocardial ischema / gene expression |
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| Research Abstract |
The cardiac ATP-sensitive potassium (K_<ATP>) channel is thought to be a complex composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the sulfonylurea receptor (SUR2). We examined the transcriptional expression of these genes in rats with myocardial ischemia. Both 60 mm of myocardial regional ischemia followed by 24-72 h of reperfusion and 24 h of continuous ischemia without reperfusion specifically upregulated Kir6.1 mRNA not only in the ischemic (2.7-3.1-fold) but also in the non-ischemic (2.0-2.6-fo1d) region of the left ventricle. In contrast, mRNAs for Kir6.2 and SUR2 remained unchanged under these ischemic procedures. Western blotting demonstrated similar increases in the Kir6.1 protein level both in the ischemic (2.4-fold) and the non-ischemic (2.2-fold) region of rat hearts subjected to 60 mm of ischemia followed by 24 h of reperfusion. These findings suggest that humoral and/or hemodynamic factors are responsible for this delayed and specific up-regulation of Kir6.1. In the next study, pretreatment with TCV-116, an angiotensin (Ang) II type .1 receptor antagonist, completely inhibited the upregulation of Kir6.1 mRNA and protein expression in both regions of rat hearts subjected to 60 mm of coronary artery occlusion followed by 24 h of reperfusion ; whereas pretreatment with lisinopril, an Ang converting enzyme (ACE) inhibitor, partly inhibited this upregulation. In addition, except for rats pretreated with TCV-116, Kir6.1 mRNA levels were positively correlated with those for brain natriuretic peptide (BNP), a molecular indicator of regional wall stress, in both the non-ischemic and the ischemic regions. Plasma Ang II levels were not elevated in rats with control myocardial ischemia compared .with sham rats. Thus, stress-induced release of tissue Ang II regulates the specific induction of cardiac Kir6.1 mRNA and protein expression under myocardial ischemia.
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