Angiotensin II drives the pathogenesis of diabetic kidney disease, and its systemic administration induces glomerular hyperpermeability in normal rats. However, the response of diabetic glomerular permeability to angiotensin II is largely unknown. In the present study, we investigated the impact of extended systemic administration of angiotensin II on the glomerular permeability of streptozotocin (STZ)-induced late diabetes in rats. We examined the changes in the glomerular permeability after subcutaneous infusion of angiotensin II at 200 ng/kg/min for 7 days into male Wistar diabetic rats with 3 months of STZ-induced diabetes (i.e., blood glucose of approximately 20 mmoL/L). We also compared these changes with the effects on nondiabetic rats. The sieving coefficients (θ) for inert polydisperse Ficoll molecules, which had a radius of 10-90 Å, were measured in vivo. The θ for large Ficoll molecules was selectively enhanced after infusion of extended angiotensin II into both diabetic (θ for Ficoll_{70-90 Å} = 0.00244 vs. 0.00079, P < 0.001) and nondiabetic animals (θ for Ficoll_{70-90 Å} = 0.00029 vs. 0.00006, p < 0.001). These changes were compatible with the more than twofold increase in the macromolecular glomerular transport through the large pore pathways after infusion of angiotensin II into both diabetic and nondiabetic animals. Angiotensin II infusion enhanced the large shunt-like glomerular transport pathway of STZ-induced late diabetes. Such defects can account for the large-molecular-weight IgM-uria that is observed in severe diabetic kidney disease.

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血管紧张素II对糖尿病肾小球高通透性的影响：大鼠体内通透性研究

血管紧张素II驱动糖尿病肾病的发病机理，其全身性给药可诱导正常大鼠的肾小球高通透性。然而，糖尿病肾小球通透性对血管紧张素II的反应在很大程度上是未知的。在本研究中，我们研究了长期全身性给药血管紧张素II对链脲佐菌素（STZ）诱导的晚期糖尿病大鼠肾小球通透性的影响。我们研究了以3个月STZ诱导的糖尿病（即血糖约为20 mmoL / L）以200 ng / kg / min的皮下输注血管紧张素II 7天给雄性Wistar糖尿病大鼠的肾小球通透性变化。我们还比较了这些变化与对非糖尿病大鼠的影响。惰性多分散Ficoll分子的筛分系数（θ），半径为10-90Å，在体内进行了测量。大剂量Ficoll分子的θ在将扩展的血管紧张素II注入糖尿病患者中后有选择地增强（Ficoll的θ_70-90 = 0.00244与0.00079，P <0.001）和非糖尿病动物（θ为聚蔗糖_70-90 = 0.00029 0.00006对比，P <0.001）。这些变化与将血管紧张素II注入糖尿病和非糖尿病动物后通过大孔通路的大分子肾小球转运增加了两倍以上是相容的。血管紧张素II输注增强了STZ诱导的晚期糖尿病的大分流状肾小球转运途径。这样的缺陷可以解释在严重的糖尿病肾病中观察到的大分子量IgM-尿。