Department of Pathology, China Medical University Affiliated Shengjing Hospital, Shenyang, PR China.
Braz J Med Biol Res. 2009 Jun;42(6):531-6. doi: 10.1590/s0100-879x2009000600009.
Angiotensin II (Ang II) plays a crucial role in the pathogenesis of renal diseases. The objective of the present study was to investigate the possible inflammatory effect of Ang II on glomerular endothelial cells and the underlying mechanism. We isolated and characterized primary cultures of rat glomerular endothelial cells (GECs) and observed that Ang II induced the synthesis of monocyte chemoattractant protein-1 (MCP-1) in GECs as demonstrated by Western blot. Ang II stimulation, at concentrations ranging from 0.1 to 10 microm, of rat GECs induced a rapid increase in the generation of reactive oxygen species as indicated by laser fluoroscopy. The level of p47phox protein, an NAD(P)H oxidase subunit, was also increased by Ang II treatment. These effects of Ang II on GECs were all reduced by diphenyleneiodonium (1.0 microm), an NAD(P)H oxidase inhibitor. Ang II stimulation also promoted the activation of nuclear factor-kappa B (NF-kappaB). Telmisartan (1.0 microm), an AT1 receptor blocker, blocked all the effects of Ang II on rat GECs. These data suggest that the inhibition of NAD(P)H oxidase-dependent NF-kappaB signaling reduces the increase in MCP-1 production by GECs induced by Ang II. This may provide a mechanistic basis for the benefits of selective AT1 blockade in dealing with chronic renal disease.
血管紧张素 II（Ang II）在肾脏疾病的发病机制中起着至关重要的作用。本研究的目的是探讨 Ang II 对肾小球内皮细胞可能产生的炎症作用及其潜在机制。我们分离并鉴定了大鼠肾小球内皮细胞（GEC）的原代培养物，并观察到 Ang II 通过 Western blot 诱导 GEC 中单核细胞趋化蛋白-1（MCP-1）的合成。Ang II 刺激浓度为 0.1 至 10 µm 的大鼠 GEC 迅速增加活性氧的产生，如激光荧光法所示。NAD（P）H 氧化酶亚基 p47phox 蛋白的水平也因 Ang II 处理而增加。Diphenyleneiodonium（1.0 µm），一种 NAD（P）H 氧化酶抑制剂，可降低 Ang II 对 GEC 的所有这些作用。Ang II 刺激还促进了核因子-κB（NF-κB）的激活。AT1 受体阻滞剂替米沙坦（1.0 µm）阻断了 Ang II 对大鼠 GEC 的所有作用。这些数据表明，抑制 NAD（P）H 氧化酶依赖性 NF-κB 信号通路可减少 Ang II 诱导的 GEC 中 MCP-1 产生的增加。这可能为选择性 AT1 阻断在处理慢性肾脏疾病方面的益处提供了机制基础。
