Angiotensin II type 1 and type 2 receptors play opposite roles in regulating the barrier function of kidney glomerular capillary wall
Angiotensin II type 1 and type 2 receptors play opposite roles in regulating the barrier function of kidney glomerular capillary wall
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DOI：
10.2353/ajpath.2007.060484
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发表时间：
2007-06-01
影响因子：
6
通讯作者：
Kawachi, Hiroshi
中科院分区：
文献类型：
--
作者：
Suzuki, Koichi;Han, Gi Dong;Kawachi, Hiroshi
尽管血管紧张素H(Ang II)1型受体拮抗剂可以改善蛋白尿，但其药理机制以及血管紧张素1型受体(AT1R)和2型受体(AT2R)的区别作用尚不清楚。我们分析了血管紧张素H 1型受体拮抗剂对肾小球裂隙隔抗体所致蛋白尿的影响，其功能障碍参与了多种肾小球疾病蛋白尿的发生。我们在这里表明，AT1R拮抗剂通过阻止裂隙隔膜功能分子的减少来改善蛋白尿。我们还分析了AT1R或AT2R介导的作用在正常大鼠体内研究和体外培养足细胞研究中对裂隙膜分子表达的影响。AT1R介导的作用抑制了缝隙膜分子的mRNA表达，而AT2R介导的作用则增强了它的表达。这些结果表明，Ang H受体亚型在调节肾小球毛细血管壁屏障功能中起相反的作用，AT2R刺激的增强可能是一种潜在的治疗蛋白尿的策略。
Although angiotensin H (Ang II) type 1 receptor antagonist ameliorates proteinuria, its pharmacological mechanism and the differential roles of Ang H type 1 receptor (AT1R) and type 2 receptor (AT2R) are not well understood. We analyzed the effect of Ang H type 1 receptor antagonist on proteinuria caused by antibody against nephrin, a functional molecule of glomerular slit diaphragm and dysfunction of which is involved in the development of proteinuria in several glomerular diseases. We show here that AT1R antagonist ameliorated proteinuria by preventing a reduction in the functional molecules of the slit diaphragm. We also analyzed the role of AT1R- or AT2R-mediated actions on the expression of the slit diaphragm molecules in an in vivo study of normal rat and in an in vitro study of cultured podocytes. AT1R-mediated action hampered the mRNA expression of the slit diaphragm molecules, whereas AT2R-mediated action enhanced it. These findings indicate that Ang H receptor subtypes play opposite roles in regulating the barrier function of glomerular capillary wall and that the enhancement of AT2R stimulation may serve as a potential therapeutic strategy for proteinuria.