| Project/Area Number |
25461241
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Horita Shoko 東京大学, 医学部附属病院, 助教 (20534895)
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| Co-Investigator(Kenkyū-buntansha) |
Suzuki Masashi 東京大学, 医学部附属病院, 助教 (90595662)
Seki Joji 東京大学, 医学部附属病院, 講師 (30206619)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 高血圧 / NO / ET / Na再吸収 / 近位尿細管 / Na輸送 / 尿細管 |
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| Outline of Final Research Achievements |
We found that Angiotensin II (AngII) induces a dose-dependent profound stimulation of human proximal tubule (PT) transport by type 1 AngII receptor (AT1)-dependent phosphorylation of ERK. In PTs of wild-type mice, NO/cGMP/cGKII pathway mediated the inhibitory effect of Ang II, while MEK/ERK pathway mediated the stimulatory effect. Conversely, in human PTs, the NO/cGMP/ERK pathway mediated the stimulatory effect of Ang II. The intracellular Ca2+ did not have any effect on PT transport in mice, but dose-dependently stimulated human PT transport. Endothelin (ET), like AngII, induced very subtle biphasic effect on mice PT, while induced a dose-dependent strong stimulation of human PT transport. These contrasting responses to the NO/cGMP pathway may largely explain the different modes of PT transport regulation by AngII, and the unopposed marked stimulation of PT transport by high intrarenal concentrations of AngII may be an important factor in the pathogenesis of human hypertension.
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