Cilnidipine suppresses podocyte injury and proteinuria in metabolic syndrome rats: possible involvement of N-type calcium channel in podocyte
Cilnidipine suppresses podocyte injury and proteinuria in metabolic syndrome rats: possible involvement of N-type calcium channel in podocyte
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DOI：
10.1097/hjh.0b013e328336ade3
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发表时间：
2010-05-01
影响因子：
4.9
通讯作者：
Nishiyama, Akira
中科院分区：
文献类型：
--
作者：
Fan, Yu-Yan;Kohno, Masakazu;Nishiyama, Akira
目的临床研究表明，L/N型钙通道阻滞剂西尼地平（cilnidipine）对高血压患者蛋白尿的进展有较好的疗效。在本研究中，我们研究了西尼地平和西尼地平对自发性高血压大鼠/ND mcr-cp（SHR/ND）肾损伤的影响及其潜在机制。n=11]或氯吡格雷（20 mg/kg/天，p.o.; n=9）20周。SHR/ND的蛋白尿发生率与年龄相关。西尼地平对蛋白尿的抑制作用大于顺铂。免疫组化结果显示N型钙通道与足细胞标志物Wilm肿瘤因子共表达。SHR/ND有显着更大的结蛋白染色，足细胞损伤的指标，与较低的podocin和nephrin表达在肾小球比Wistar-Kyoto大鼠或SHR。西尼地平显著阻止结蛋白染色的增加，并恢复肾小球podocin和nephrin表达。西尼地平还可抑制SHR/ND肾脏血管紧张素II含量的增加、NADPH氧化酶亚基的表达和膜转位以及二氢乙锭染色。结论西尼地平可能通过抑制N型钙通道依赖性足细胞损伤，抑制SHR/ND大鼠蛋白尿的发生。J Hypertens 28：1034-1043（C）2010 Wolters Kluwer Health竖条Lippincott威廉姆斯& Wilkins.
Objectives Clinical studies have indicated the beneficial effect of an L/N-type calcium channel blocker (CCB), cilnidipine, on the progression of proteinuria in hypertensive patients compared with an L-type CCB, amlodipine. In the present study, we examined the effects of cilnidipine and amlodipine on the renal injury in spontaneously hypertensive rat/ND mcr-cp (SHR/ND) and their underlying mechanism.Methods and results SHR/ND were treated with vehicle (n=10), cilnidipine [33 mg/kg per day, orally (p.o.); n=11] or amlodipine (20 mg/kg per day, p.o.; n=9) for 20 weeks. SHR/ND developed proteinuria in an age-dependent manner. Cilnidipine suppressed the proteinuria greater than amlodipine did. The immunohistochemical analysis showed that N-type calcium channel and Wilm's tumor factor, a marker of podocyte, were co-expressed. SHR/ND had significantly greater desmin staining, an indicator of podocyte injury, with lower podocin and nephrin expression in the glomeruli than Wistar-Kyoto rat or SHR. Cilnidipine significantly prevented the increase in desmin staining and restored the glomerular podocin and nephrin expression compared with amlodipine. Cilnidipine also prevented the increase in renal angiotensin II content, the expression and membrane translocation of NADPH oxidase subunits and dihydroethidium staining in SHR/ND. In contrast, amlodipine failed to change these renal parameters.Conclusion These data suggest that cilnidipine suppressed the development of proteinuria greater than amlodipine possibly through inhibiting N-type calcium channel-dependent podocyte injury in SHR/ND. J Hypertens 28:1034-1043 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.