| Project/Area Number |
14570097
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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 |
General pharmacology
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| Research Institution | Fukuoka University (2003)
National Cardiovascular Center Research Institute (2002) |
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Principal Investigator |
IWAMOTO Takahiro Fukuoka University, School of Medicine, Lecturer, 医学部, 講師 (20300973)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Na^+ / Ca^<2+> exchanger / Hypertension / Calcium ion / Salt-sensitivity / Vasodilation / トランスジェニックマウス / 食塩感受性高血圧 / 心肥大 / 血管肥厚 / 腎臓障害 / 血管拡張 |
|---|
| Research Abstract |
Excessive salt intake is a major risk factor for hypertension Here we identify the role of Na^+/Ca^<2+> exchanger type 1 (NCX1) in salt-sensitive hypertension using SEA0400, a specific inhibitor for Ca^<2+> entry via NCX1, and genetically engineered mice. SEA0400 lowers arterial blood pressure in salt-dependent hypertensive rat models, but not in normotensive rats or other types of hypertensive rats. Infusion of SEA0400 into the femoral artery in salt-dependent hypertensive rats increases arterial blood flow indicating peripheral vasodilation. SEA0400 reverses ouabain-induced cytosolic Ca^<2+> elevation and vasoconstriction in arteries. Furthermore, heterozygous NCX1-deflcient mice have low salt-sensitivity, whereas transgenic mice that specifically express NCX1.3 in smooth muscle are hypersensitive to salt SEA0400 significantly lowers the blood pressure in salt-dependent hypertensive mice expressing NCX1.3, but not in SEA0400-insensitive NCX1.3 mutants. These findings indicate that salt-sensitive hypertension is triggered by Ca^<2+> entry via NCX1 in arterial smooth muscle and suggest that NCX1 inhibitors might be useful therapeutically.
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