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.

目前的研究旨在确定葡萄糖和胰岛素对肾血流以及高血压的调节和发育的作用。用激光多普勒流量指定在麻醉大鼠中确定局部肾血流。 50％葡萄糖的静脉输注显着提高了血糖水平，并使肾脏血流降低了约20％。这种反应通过肾脏间隙输注超氧化物清除剂Tiron减弱。静脉输注50％葡萄糖后胰岛素的间质输注不会改变髓样血流。但是，当将50％的葡萄糖直接注入肾脏间质时，髓样流量减少而没有血糖水平的变化。这些结果表明，血糖的增加会诱导肾脏氧化应激并减少髓质血流，从而产生高血压。在Dahl盐敏感（DAHLS）大鼠，DAHL盐耐盐（DAHLR）大鼠和Sprague-Dawley（Sdawley（Sd）中，饮用水中的10％蔗糖在饮用水中服用。在蔗糖负荷后一周的DAHL和DAHLR大鼠中观察到血压的升高，但是，在两周内，SD大鼠的血压没有明显升高。用Angiontensin II受体阻滞剂阻断了蔗糖诱导的DAHLS中的高血压。所有组的尿液过氧化氢排泄作为氧化应激的指标均增加，但SD大鼠的氧化应激量均明显较小。通过施用Na-葡萄糖共转运蛋白（SGLT）磷酸蛋白，使血压和尿过氧化氢排泄的升高减弱。此外，肾脏间质输注硫氟蛋白抑制了50％葡萄糖的急性静脉输注减少髓样血流。我们得出的结论是，血糖的增加降低了髓样血流，并通过SGLT和肾素血管紧张素系统增强氧化应激而发展高血压。