| Project/Area Number |
17590181
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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 physiology
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| Research Institution | Tohoku University |
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Principal Investigator |
MORI Takefumi Center for the Advancement of Higher Education, Tohoku University, assistant professor, 高等教育開発推進センター, 助手 (40375001)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Sadayoshi Tohoku University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (40271613)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Glucose / Insulin / Diabetes / Hypertension / Oxidative stress / Renal blood flow / Renal tubules / 腎障害 |
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| Research Abstract |
Present study was designed to determine the role of glucose and insulin to the renal blood flow and regulation and development of hypertension. Local renal blood flow was determined in anesthetized rats with laser Doppler flowmetry. Intravenous infusion of 50% glucose significantly increased blood glucose level and reduced renal medullary blood flow by approximately 20%. This response was attenuated by renal interstitial infusion of superoxide scavenger Tiron. Interstitial infusion of insulin after intravenous infusion of 50% glucose did not alter medullary blood flow. However, when 50% glucose was infused directly into renal interstitium, medullary blood flow reduced with no change in blood glucose level. These results indicate that increase in blood glucose induce renal oxidative stress and reduce medullary blood flow, thereby develop hypertension.
Next, 10% sucrose in drinking water were administered in Dahl salt sensitive (DahlS) rats, Dahl salt resistant (DahlR) rats and Sprague-Dawley (SD) rats for two weeks. Increase in blood pressure was observed in DahlS and DahlR rats from one week after sucrose loading, however, no significant increase in blood pressure was observed in those of SD rats over two weeks. Sucrose induced hypertension in DahlS was blocked with angiontensin II receptor blocker. Urinary hydrogen peroxide excretion as a indicator of oxidative stress was increased in all groups but was significantly smaller in SD rats. Increase in blood pressure and urinary hydrogen peroxide excretion was attenuated by administration of Na-glucose cotransporter (SGLT) phlorizin. Moreover, renal interstitial infusion of phlorizin inhibited the reduction of medullary blood flow with acute intravenous infusion of 50% glucose. We conclude that increase in blood glucose reduce medullary blood flow and develop hypertension by enhanced oxidative stress via SGLT and renin angiotensin system.
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