Roos M H, Eringa E C, van Rodijnen W F, van Lambalgen T A, Ter Wee P M, Tangelder G J
Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
Diabetes Obes Metab. 2008 Sep;10(10):898-905. doi: 10.1111/j.1463-1326.2007.00827.x. Epub 2007 Dec 17.
Obesity in humans is associated with proteinuria and an increased glomerular filtration, possibly related to an increase in glomerular capillary pressure. We investigated in obese and lean Zucker rats (10-12 weeks old) whether this might be related to alterations in the diameter of preglomerular and postglomerular microvessels and their reactivity to the resistance regulator angiotensin II (AngII), using the hydronephrotic kidney model.
The obese rats exhibited a hyperinsulinaemic, euglycaemic state and hypertension. Urinary protein concentration and fluid intake were both increased threefold. Basal diameters of distal interlobular arteries (ILAs) and afferent arterioles (AAs) were larger in the obese rat than in the lean rat (ILA: 25.7 +/- 0.3 vs. 23.0 +/- 0.4 microm and AA: 18.8 +/- 0.3 vs. 16.7 +/- 0.5 microm, respectively; p </= 0.01), while diameters of efferent arterioles (EAs) were smaller in obese animals (14.2 +/- 1.1 vs. 18.2 +/- 1.2 microm; p </= 0.05). AngII induced a concentration-dependent constriction in ILA, AA and EA with an augmented response in the obese compared with the lean rats. Thus, at higher concentrations, AngII abolished the diameter difference between obese and lean animals in preglomerular microvessels while exaggerating that in postglomerular arterioles.
Our data indicate that in obese rats, a vasodilated state in small preglomerular microvessels and a vasoconstricted state in the postglomerular arterioles exist. Although AngII cancelled the former, the latter remained. Therefore, these data reveal periglomerular vascular changes that may play a role in glomerular dysfunction and renal pathology associated with obesity.
人类肥胖与蛋白尿及肾小球滤过增加有关，这可能与肾小球毛细血管压力升高有关。我们使用肾积水肾脏模型，研究了肥胖和瘦型 Zucker 大鼠（10 - 12 周龄）中，这是否可能与肾小球前和肾小球后微血管直径的改变及其对阻力调节因子血管紧张素 II（AngII）的反应性有关。
肥胖大鼠呈现高胰岛素血症、血糖正常状态和高血压。尿蛋白浓度和液体摄入量均增加了两倍。肥胖大鼠的小叶间远端动脉（ILA）和入球小动脉（AA）的基础直径大于瘦型大鼠（ILA：25.7 ± 0.3 对 23.0 ± 0.4 微米，AA：18.8 ± 0.3 对 16.7 ± 0.5 微米，分别；p ≤ 0.01），而肥胖动物的出球小动脉（EA）直径较小（14.2 ± 1.1 对 18.2 ± 1.2 微米；p ≤ 0.05）。AngII 在 ILA、AA 和 EA 中诱导浓度依赖性收缩，与瘦型大鼠相比，肥胖大鼠的反应增强。因此，在较高浓度下，AngII 消除了肥胖和瘦型动物在肾小球前微血管中的直径差异，同时夸大了肾小球后小动脉中的差异。
我们的数据表明，在肥胖大鼠中，存在肾小球前小微血管的血管舒张状态和肾小球后小动脉的血管收缩状态。尽管 AngII 消除了前者，但后者仍然存在。因此，这些数据揭示了肾小球周围血管变化，可能在与肥胖相关的肾小球功能障碍和肾脏病理中起作用。
