De Vriese A S, Stoenoiu M S, Elger M, Devuyst O, Vanholder R, Kriz W, Lameire N H
Renal Unit, Gent University, Gent, and Renal Unit, Université Catholique de Louvain, Brussels, Belgium.
Kidney Int. 2001 Jul;60(1):202-10. doi: 10.1046/j.1523-1755.2001.00787.x.
Renal hemodynamics in early diabetes are characterized by preglomerular and postglomerular vasodilation and increased glomerular capillary pressure, leading to hyperfiltration. Despite intensive research, the etiology of the renal vasodilation in diabetes remains a matter of debate. The present study investigated the controversial role of nitric oxide (NO) in the renal vasodilation in streptozotocin-induced diabetic rats.
In the renal microcirculation, basal tone and response to NO synthase blockade were studied using the in vivo hydronephrotic kidney technique. L-arginine analog N-nitro-L-arginine methyl ester (L-NAME) was administered locally to avoid confounding by systemic blood pressure effects. The expression of endothelial NO synthase (eNOS) was investigated in total kidney by immunocytochemistry and in isolated renal vascular trees by Western blotting. Urinary excretion of nitrites/nitrates was measured.
Diabetic rats demonstrated a significant basal vasodilation of all preglomerular and postglomerular vessels versus control rats. Vasoconstriction to L-NAME was significantly increased in diabetic vessels. After high-dose L-NAME, there was no difference in diameter between diabetic and control vessels, suggesting that the basal vasodilation is mediated by NO. Immunocytochemically, the expression of eNOS was mainly localized in the endothelium of preglomerular and postglomerular vessels and glomerular capillaries, and was increased in the diabetic kidneys. Immunoblots on isolated renal vascular trees revealed an up-regulation of eNOS protein expression in diabetic animals. The urinary excretion of nitrites/nitrates was elevated in diabetic rats.
The present study suggests that an up-regulation of eNOS in the renal microvasculature, resulting in an increased basal generation of NO, is responsible for the intrarenal vasodilation characteristic of early diabetes.
早期糖尿病患者的肾血流动力学特征为肾小球前和肾小球后血管舒张以及肾小球毛细血管压力升高，导致超滤过。尽管进行了深入研究，但糖尿病患者肾血管舒张的病因仍存在争议。本研究探讨了一氧化氮（NO）在链脲佐菌素诱导的糖尿病大鼠肾血管舒张中的争议性作用。
在肾微循环中，使用体内肾积水肾脏技术研究基础张力和对NO合酶阻断的反应。局部给予L-精氨酸类似物N-硝基-L-精氨酸甲酯（L-NAME）以避免全身血压影响造成混淆。通过免疫细胞化学在全肾中以及通过蛋白质印迹法在分离的肾血管树中研究内皮型NO合酶（eNOS）的表达。测量尿中亚硝酸盐/硝酸盐的排泄量。
与对照大鼠相比，糖尿病大鼠所有肾小球前和肾小球后血管均表现出明显的基础血管舒张。糖尿病血管对L-NAME的血管收缩反应明显增强。高剂量L-NAME后，糖尿病血管和对照血管的直径没有差异，表明基础血管舒张是由NO介导的。免疫细胞化学显示，eNOS的表达主要定位于肾小球前和肾小球后血管以及肾小球毛细血管的内皮中，并且在糖尿病肾脏中增加。对分离的肾血管树进行的蛋白质印迹显示糖尿病动物中eNOS蛋白表达上调。糖尿病大鼠尿中亚硝酸盐/硝酸盐的排泄量升高。
本研究表明，肾微血管中eNOS上调导致基础NO生成增加，这是早期糖尿病肾内血管舒张的原因。
