Becker B N, Yasuda T, Kondo S, Vaikunth S, Homma T, Harris R C
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2372, USA.
Exp Nephrol. 1998 Jan-Feb;6(1):57-66. doi: 10.1159/000020505.
Angiotensin II (Ang II) may play a significant role mediating intraglomerular hypertension and glomerular sclerosis. Therefore, we investigated whether a model of pressure-induced stress, mechanical stretch/relaxation, affected the renin-angiotensin system (RAS) in cultured rat mesangial cells. Type 1 Ang II receptor (AT1R) expression was assessed by 125I-Ang II binding and quantitative reverse-transcription polymerase chain reaction. Stretch/relaxation increased steady-state AT1R mRNA levels as well as specific [125I]Ang II binding. Increased AT1R expression was associated with altered AT1R signaling. Ang II (100 nM) increased total phosphoinositide hydrolysis in control cells (186 +/- 25%, n = 6; p < 0.025 vs. no treatment). However, stretch/relaxation for 48 h further augmented AT1R-mediated PI hydrolysis (293 +/- 38%, n = 6; p < 0.025 vs. Ang II treatment alone). We examined other RAS components in mesangial cells subjected to stretch/relaxation. Angiotensinogen, determined by radioimmunoassay of Ang I generation in conditioned media, increased with stretch/relaxation, and reverse-transcription polymerase chain reaction demonstrated increased angiotensinogen gene expression in stretch/relaxation-treated cells. However, renin activity and angiotensin-converting-enzyme-like activity were unaffected by stretch/relaxation. Thus, mesangial cells maintain a local RAS similar to those described in other tissues, and AT1R expression and angiotensinogen production in this cellular RAS are increased by stretch/relaxation. It is likely that mesangial cells in vivo, exposed to variations in intraglomerular pressure, may regulate their responses via a local RAS.
血管紧张素II（Ang II）可能在介导肾小球内高压和肾小球硬化中发挥重要作用。因此，我们研究了压力诱导应激模型，即机械拉伸/松弛，是否会影响培养的大鼠系膜细胞中的肾素-血管紧张素系统（RAS）。通过125I-Ang II结合和定量逆转录聚合酶链反应评估1型Ang II受体（AT1R）的表达。拉伸/松弛增加了稳态AT1R mRNA水平以及特异性[125I]Ang II结合。AT1R表达增加与AT1R信号传导改变有关。Ang II（100 nM）增加了对照细胞中的总磷酸肌醇水解（186±25%，n = 6；与未处理相比，p < 0.025）。然而，48小时的拉伸/松弛进一步增强了AT1R介导的PI水解（293±38%，n = 6；与单独Ang II处理相比，p < 0.025）。我们检查了经受拉伸/松弛的系膜细胞中的其他RAS成分。通过对条件培养基中Ang I生成的放射免疫测定确定的血管紧张素原随着拉伸/松弛而增加，逆转录聚合酶链反应表明在经拉伸/松弛处理的细胞中血管紧张素原基因表达增加。然而，肾素活性和血管紧张素转换酶样活性不受拉伸/松弛的影响。因此，系膜细胞维持与其他组织中描述的类似的局部RAS，并且该细胞RAS中的AT1R表达和血管紧张素原产生通过拉伸/松弛而增加。体内暴露于肾小球内压力变化的系膜细胞可能通过局部RAS调节其反应。
