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

本研究旨在探讨葡萄糖和胰岛素对肾血流量的影响以及对高血压的调节和发展的作用。用激光多普勒血流仪测定麻醉大鼠局部肾血流量。静脉输注50%葡萄糖显著升高血糖水平，并使肾髓质血流量减少约20%。这种反应减弱肾间质灌注超氧化物清除剂Tiron。静脉输注50%葡萄糖后间质输注胰岛素并不改变髓质血流。然而，当50%葡萄糖直接注入肾髓质时，髓质血流量减少，血糖水平无变化。这些结果表明，血糖升高引起肾氧化应激和髓血流量减少，从而发展为高血压。接下来，在Dahl盐敏感（DahlS）大鼠、Dahl盐抵抗（DahlR）大鼠和Sprague-Dawley（SD）大鼠中给予饮用水中的10%蔗糖两周。在DahlS和DahlR大鼠中，从蔗糖负荷后一周起观察到血压升高，然而，在SD大鼠中，在两周内没有观察到血压显著升高。用血管紧张素II受体阻断剂阻断蔗糖诱导的DahlS高血压。尿过氧化氢排泄作为氧化应激的指标在所有组中均增加，但在SD大鼠中显着较小。钠-葡萄糖协同转运蛋白（SGLT）根皮苷给药可降低血压和尿过氧化氢排泄量。此外，肾间质灌注根皮苷抑制急性静脉输注50%葡萄糖引起的髓质血流量减少。我们的结论是，血糖增加减少髓血流量，并通过SGLT和肾素血管紧张素系统增强氧化应激发展高血压。

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.