| Project/Area Number |
17K16010
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 高血圧症 / 慢性腎臓病 / 腎除神経術 / アンジオテンシンⅡ受容体拮抗薬 / 中枢性交感神経調節 / 中枢性交感神経活動 / 心不全 / 腎除神経 / 中枢性循環調節 / 交感神経活動 |
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| Outline of Final Research Achievements |
Augmented sympathetic nerve activity (SNA) is involved in the pathogenesis of hypertension (HT) accompanied by chronic kidney disease (CKD). Oxidative stress in the cardiovascular center in the brain increases SNA in HT. Administration of an angiotensin Ⅱ receptor blocker (ARB) or renal denervation (RDN) exerts an antihypertensive effect in HT with CKD; however, the precise mechanisms of the combination therapy are not fully elucidated.
In the present study, 5/6-nephrectomized mice (Nx-mice) presented HT, accompanied by increased SNA and albuminuria. Nx-mice were orally administered ARB (Nx-ARB) or underwent RDN during ARB administration (Nx-ARB/RDN). In Nx-ARB/RDN, blood pressure (BP) was decreased greater than that in Nx-ARB and both SNA and oxidative stress levels in the brain were suppressed.
In conclusion, the combination therapy with ARB/RDN has antihypertensive effects in association with suppressing SNA by reducing oxidative stress in the brain in hypertensive mice with CKD.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病に合併する高血圧はしばしば治療抵抗性であり、その機序に交感神経活動の活性化が示唆されている。今回の研究では慢性腎臓病合併高血圧モデルへのアンジオテンシンⅡ受容体拮抗薬(ARB)と腎除神経術(RDN)の併用により強力な降圧効果、脳内酸化ストレス抑制に伴う交感神経活動低下を認めた。今回の成果により当併用療法が慢性腎臓病合併高血圧患者に対する有用な治療選択肢になり得ると考えられる。
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