Bertels Ivome M V, Gontijo José A R, Figueiredo José F
Organ Preservation Laboratories, Medical Sciences School, State University of Campinas-Unicamp, Campinas - Brazil.
J Nephrol. 2007 Jan-Feb;20(1):29-35.
The response of proximal convoluted tubules (PCTs) to angiotensin II is mediated by specific type 1 receptors found on both apical and basolateral surface membrane cells. After ligand association with type 1 receptors, different signaling pathways are triggered and determine changes in fluid absorption (Jv). The presence of AT1 and actin cytoskeleton, which are directly related to Jv, can undergo changes in distribution based on the actions of AngII and losartan.
Using a microperfusion technique and immunohistochemistry analysis, we investigated the basolateral action in PCTs, of AngII and/or losartan on Jv in rabbits, with regard to AT1 and actin cytoskeleton.
AngII increased Jv, while in contrast, losartan and combined AngII + losartan led to its decrease. AngII did not change fluorescence intensity of AT1 receptors on tubular membranes, while losartan and AngII + losartan demonstrated a slight increase after treatment. On the other hand, AngII increased the fluorescence intensity of actin cytoskeleton, while losartan induced a decrease. AngII + losartan led actin cytoskeleton having a higher fluorescence intensity than in the control group.
In the present study, we demonstrated that treatment of the basolateral side of PCT cells with AngII and losartan could lead to changes in absorptive tubular function. Important alterations were detected in AT1 receptor fluorescence on the luminal and basolateral membranes, and changes in F-actin cytoskeleton were verified by fluorescence following these protocols.
近端肾小管(PCT)对血管紧张素II的反应是由位于顶端和基底外侧表面膜细胞上的特定1型受体介导的。配体与1型受体结合后,会触发不同的信号通路并决定液体吸收(Jv)的变化。与Jv直接相关的AT1和肌动蛋白细胞骨架的存在,会根据血管紧张素II和氯沙坦的作用而发生分布变化。
我们使用微灌注技术和免疫组织化学分析,研究了血管紧张素II和/或氯沙坦对兔PCT中Jv的基底外侧作用,涉及AT1和肌动蛋白细胞骨架。
血管紧张素II增加了Jv,而相比之下,氯沙坦以及血管紧张素II与氯沙坦联合使用则导致Jv降低。血管紧张素II未改变肾小管膜上AT1受体的荧光强度,而氯沙坦和血管紧张素II +氯沙坦在处理后显示略有增加。另一方面,血管紧张素II增加了肌动蛋白细胞骨架的荧光强度,而氯沙坦则使其降低。血管紧张素II +氯沙坦导致肌动蛋白细胞骨架的荧光强度高于对照组。
在本研究中,我们证明用血管紧张素II和氯沙坦处理PCT细胞的基底外侧可导致肾小管吸收功能发生变化。在管腔和基底外侧膜上检测到AT1受体荧光有重要改变,并且按照这些方案通过荧光验证了F-肌动蛋白细胞骨架的变化。