Role of glucose and insulin to regulation of renal circulation and development of hypertension.

葡萄糖和胰岛素在调节肾循环和高血压发展中的作用。

基本信息

批准号：
17590181
负责人：
MORI Takefumi
金额：
$ 2.3万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590181/
关键词：
Glucose Insulin Diabetes Hypertension Oxidative stress Renal blood flow Renal tubules 腎障害

项目摘要

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.

本研究旨在确定葡萄糖和胰岛素对肾血流量以及高血压的调节和发展的作用。用激光多普勒血流计测定麻醉大鼠的局部肾血流量。静脉输注50%葡萄糖显着升高血糖水平，并使肾髓质血流量减少约20%。这种反应通过肾间质输注超氧化物清除剂Tiron而减弱。静脉输注50%葡萄糖后间质输注胰岛素不会改变髓质血流。然而，当50%葡萄糖直接注入肾间质时，髓质血流量减少，但血糖水平没有变化。这些结果表明，血糖升高会诱发肾脏氧化应激，减少髓质血流量，从而发展为高血压。接下来，对达尔盐敏感（DahlS）大鼠、达尔盐抗性（DahlR）大鼠和斯普拉格（Sprague）大鼠给予饮用水中的10％蔗糖-Dawley (SD) 大鼠两周。从蔗糖负荷1周起，DahlS和DahlR大鼠的血压升高，但SD大鼠两周后血压没有明显升高。 DahlS 中蔗糖诱导的高血压被血管紧张素 II 受体阻滞剂阻断。作为氧化应激指标的尿液过氧化氢排泄量在所有组中均有所增加，但在 SD 大鼠中显着减少。给予钠-葡萄糖协同转运蛋白（SGLT）根皮苷可减弱血压和尿过氧化氢排泄的增加。此外，肾间质输注根皮苷可抑制急性静脉输注50%葡萄糖引起的髓质血流量的减少。我们得出的结论是，血糖升高会减少髓质血流量，并通过 SGLT 和肾素血管紧张素系统增强氧化应激而发展为高血压。