Effects of dietary salt on intrarenal angiotensin system, NAD(P)H oxidase, COX-2, MCP-1 and PAI-1 expressions and NF-κB activity in salt-sensitive and -resistant rat kidneys
Effects of dietary salt on intrarenal angiotensin system, NAD(P)H oxidase, COX-2, MCP-1 and PAI-1 expressions and NF-κB activity in salt-sensitive and -resistant rat kidneys
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DOI：
10.1159/000110021
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Vaziri, N. D.
中科院分区：
文献类型：
--
作者：
Chandramohan, G.;Bai, Y.;Vaziri, N. D.
背景资料：高盐饮食的慢性消耗导致高血压（HTN）和肾损伤的达尔盐敏感（SSR），但不耐盐大鼠（SRR）。这些事件部分由肾脏和血管组织中的氧化应激和炎症介导。血管紧张素II 1型（AT（1））受体的激活在许多高血压疾病的氧化应激和炎症的发病机制中起重要作用。然而，盐敏感性HTN患者的全身性肾素-血管紧张素系统（RAS）通常受到抑制。本研究旨在验证以下假设：SSR与SRR对高盐饮食的差异反应可能与组织RAS的上调以及炎症和活性氧（ROS）产生相关的途径有关。方法和结果：在食用高盐（8%）或低盐（0.07%）饮食3周后研究SSR和SRR。与SRR组相比，低盐饮食的SSR组肾脏AT（1）受体、环氧合酶（考克斯）2、纤溶酶原激活物抑制剂（派）和磷酸化I κ B水平显著升高。高盐饮食导致严重的HTN和蛋白尿（在SSR中，而不是SRR中），SSR组肾组织单核细胞趋化蛋白1、p22（phox）、NADPH氧化酶亚基4、血管紧张素II阳性细胞计数、浸润T细胞和巨噬细胞显著升高，AT（1）受体、考克斯-2、派-1和磷酸化I κ B进一步升高。高盐饮食显着降低血浆肾素活性（PRA）在SRR，但不是在SSR。两组中，低盐饮食组的考克斯-1丰度相似，高盐饮食组的上升幅度相同。在喂低盐饮食的动物亚组中，SSR组的肾脏谷胱甘肽过氧化物酶（GPX）丰度显著低于SRR组。高盐饮食提高了GPX和线粒体超氧化物歧化酶（SOD）的丰度在SRR肾脏，但未能做到这一点在SSR。低盐组SSR和SRR的Cu/Zn-SOD丰度相近。高盐日粮导致SSR中Cu/Zn-SOD活性下调，但对SRR无影响。结论：SSR中的盐敏感性与肾内血管紧张素系统、ROS生成和促炎/促纤维化蛋白的上调以及不能提高抗氧化酶和最大限度地抑制PRA以响应高盐摄入相关。这些事件可导致SSR患者高盐摄入引起的肾损伤。版权所有（c）2007 S. Karger AG，巴塞尔。
Background: Chronic consumption of a high-salt diet causes hypertension (HTN) and renal injury in Dahl salt-sensitive (SSR) but not salt-resistant rats (SRR). These events are, in part, mediated by oxidative stress and inflammation in the kidney and vascular tissues. Activation of the angiotensin II type 1 (AT(1)) receptor plays an important role in the pathogenesis of oxidative stress and inflammation in many hypertensive disorders. However, the systemic renin-angiotensin system (RAS) is typically suppressed in salt-sensitive HTN. This study was designed to test the hypothesis that differential response to a high-salt diet in SSR versus SRR may be related to upregulation of tissue RAS and pathways involved in inflammation and reactive oxygen species (ROS) production. Methods and Results: SSR and SRR were studied 3 weeks after consumption of high- (8%) or low-salt (0.07%) diets. The SSR consuming a low-salt diet exhibited significant increases in AT(1) receptor, cyclooxygenase (COX) 2, plasminogen activator inhibitor (PAI) and phospho-I kappa B in the kidney as compared to those found in SRR. The high-salt diet resulted in severe HTN and proteinuria (in SSR but not SRR) and marked elevations of renal tissue monocyte chemoattractant protein 1, p22(phox), NADPH oxidase subunit 4, angio-tensin-II-positive cell count, infiltrating T cells and macrophages and further increases in AT(1) receptor, COX-2, PAI-1 and phospho-I kappa B in the SSR group. The high-salt diet significantly lowered plasma renin activity (PRA) in SRR but not in the SSR. COX-1 abundance was similar on the low-salt diet and rose equally with the high-salt diet in both groups. Among subgroups of animals fed the low-salt diet, kidney glutathione peroxidase (GPX) abundance was significantly lower in the SSR than SRR. The high-salt diet raised GPX and mitochondrial superoxide dismutase (SOD) abundance in the SRR kidneys but failed to do so in SSR. Cu/Zn-SOD abundance was similar in the subgroups of SSR and SRR fed the low-salt diet. The high-salt diet resulted in downregulation of Cu/Zn-SOD in SSR but not SRR. Conclusions: Salt sensitivity in the SSR is associated with upregulations of the intrarenal angiotensin system, ROS-generating and proinflammatory/ profibrotic proteins and an inability to raise antioxidant enzymes and maximally suppress PRA in response to high salt intake. These events can contribute to renal injury with high salt intake in SSR. Copyright (c) 2007 S. Karger AG, Basel.