Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Acta Physiol (Oxf). 2019 May;226(1):e13254. doi: 10.1111/apha.13254. Epub 2019 Feb 5.
Common kidney alterations early after the onset of insulinopenic diabetes include glomerular hyperfiltration, increased oxygen consumption and tissue hypoxia. Increased activity of the renin-angiotensin-aldosterone system (RAAS) has been implicated in most of these early alterations. The RAAS peptide angiotensin (1-7) has the potential to modulate RAAS-mediated alterations in kidney function. Thus, the aim of the present study was to determine the acute effects of angiotensin (1-7) in the kidney of insulinopenic type 1 diabetic rat and the results compared to that of normoglycaemic controls.
Renal haemodynamics and oxygen homeostasis were measured 3 weeks after administration of streptozotocin before and after acute intrarenal infusion of angiotensin (1-7) at a dose of 400 ng min .
Arterial pressure and renal blood flow were similar between groups and not affected by exogenous angiotensin (1-7). Diabetics presented with glomerular hyperfiltration, increased urinary sodium excretion and elevated kidney oxygen consumption. Angiotensin (1-7) infusion normalized glomerular filtration, increased urinary sodium excretion, decreased proximal tubular reabsorption, and elevated kidney oxygen consumption even further. The latter resulting in tubular electrolyte transport inefficiency. Angiotensin (1-7) did not affect tissue oxygen tension and had no significant effects in controls on any of the measured parameters.
Diabetes results in increased responsiveness to elevated levels of angiotensin (1-7) which is manifested as inhibition of tubular sodium transport and normalization of glomerular filtration. Furthermore, elevated angiotensin (1-7) levels increase kidney oxygen consumption in the diabetic kidney even further which affects tubular electrolyte transport efficiency negatively.
胰岛素缺乏型糖尿病发病早期常见的肾脏改变包括肾小球高滤过、耗氧量增加和组织缺氧。肾素-血管紧张素-醛固酮系统（RAAS）的活性增加与这些早期改变有关。RAAS 肽血管紧张素（1-7）具有调节 RAAS 介导的肾功能改变的潜力。因此，本研究旨在确定血管紧张素（1-7）在胰岛素缺乏型 1 型糖尿病大鼠肾脏中的急性作用，并将结果与正常血糖对照组进行比较。
在链脲佐菌素给药 3 周后，测量肾脏血液动力学和氧平衡，然后在急性肾内输注血管紧张素（1-7）（400ng/min）前后进行测量。
两组之间的动脉压和肾血流量相似，外源性血管紧张素（1-7）不影响其变化。糖尿病患者表现为肾小球高滤过、尿钠排泄增加和肾脏耗氧量增加。血管紧张素（1-7）输注使肾小球滤过率正常化，增加尿钠排泄，减少近端肾小管重吸收，并使肾脏耗氧量进一步升高。后者导致肾小管电解质转运效率降低。血管紧张素（1-7）不影响组织氧张力，在对照组中对任何测量参数均无显著影响。
糖尿病导致对升高的血管紧张素（1-7）水平的反应性增加，表现为抑制肾小管钠转运和肾小球滤过率正常化。此外，升高的血管紧张素（1-7）水平进一步增加糖尿病肾脏的耗氧量，从而对肾小管电解质转运效率产生负面影响。
