Enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats
Enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats
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DOI：
10.1161/01.hyp.0000135678.20725.54
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发表时间：
2004-08-01
期刊：
影响因子：
8.3
通讯作者：
Navar, LG
中科院分区：
文献类型：
--
作者：
Prieto-Carrasquero, MC;Harrison-Bernard, LM;Navar, LG
远端肾素可能为近端血管紧张素原生成血管紧张素（Ang） I提供了可能的途径。为了研究Ang II对远端肾素的影响，我们比较了对照组和注入Ang II的大鼠肾素蛋白和mRNA的表达。采用免疫组织化学、Western blot、逆转录聚合酶链式反应（RT-PCR）和实时定量RT-PCR方法对假手术大鼠（n = 9）和注射Ang ii （80 ng/kg / min, 13 d, n = 10）的Sprague-Dawley大鼠肾脏进行处理。Ang II输注增加收缩压（181 +/- 4 vs 115 +/- 5 mm Hg），抑制血浆和肾皮质肾素活性。与假手术相比，注射Ang ii的大鼠肾小球旁器（JGA）细胞的肾素免疫反应性被抑制（0.1 +/- 0.1 vs 1.0 +/- 0.1），但远端肾元段的肾素免疫反应性增加（6.4 +/- 1.4 vs 1.0 +/- 0.1皮质；2.5 +/- 0.3 vs 1.0 +/- 0.2髓质）。小管肾素免疫染色主要分布在与水通道蛋白-2共定位的连接小管、皮质和髓质收集管的主要细胞中。与假手术组相比，注射Ang ii的大鼠肾皮质的肾素蛋白水平降低（0.4 +/- 0.2 vs 1.0 +/- 0.4），但肾髓质的肾素蛋白水平较高（1.2 +/- 0.4 vs 1.0 +/- 0.1）。在肾髓质中，RT-PCR和实时荧光定量PCR显示两组肾素转录水平相似。总之，在缺乏JGA的肾髓质中检测肾素mRNA，表明局部合成而不是摄取JGA肾素。与Ang II对JGA肾素的抑制作用相反，Ang II输注刺激集管中肾素蛋白表达，维持髓质中肾素转录水平，这可能是Ang II依赖性高血压患者肾内Ang II水平升高的原因。
Distal nephron renin may provide a possible pathway for angiotensin (Ang) I generation from proximally delivered angiotensinogen. To examine the effects of Ang II on distal nephron renin, we compared renin protein and mRNA expression in control and Ang II-infused rats. Kidneys from sham (n = 9) and Ang II-infused (80 ng/kg per minute, 13 days, n = 10) Sprague-Dawley rats were processed by immunohistochemistry, Western blot, reverse transcriptase-polymerase chain reaction (RT-PCR), and quantitative real-time RT-PCR. Ang II infusion increased systolic blood pressure (181 +/- 4 versus 115 +/- 5 mm Hg) and suppressed plasma and kidney cortex renin activity. Renin immunoreactivity was suppressed in juxtaglomerular apparatus (JGA) cells in Ang II-infused rats compared with sham (0.1 +/- 0.1 versus 1.0 +/- 0.1 relative ratio) but increased in distal nephron segments (6.4 +/- 1.4 versus 1.0 +/- 0.1 cortex; 2.5 +/- 0.3 versus 1.0 +/- 0.2 medulla). Tubular renin immunostaining was apically distributed in principal cells colocalizing with aquaporin-2 in connecting tubules and cortical and medullary collecting ducts. Renin protein levels were decreased in the kidney cortex of Ang II-infused rats compared with that of sham (0.4 +/- 0.2 versus 1.0 +/- 0.4) rats but higher in the kidney medulla (1.2 +/- 0.4 versus 1.0 +/- 0.1). In kidney medulla, RT-PCR and quantitative real-time PCR showed similar levels of renin transcript in both groups. In summary, the detection of renin mRNA in the renal medulla, which is devoid of JGA, indicates local synthesis rather than an uptake of JGA renin. In contrast to the inhibitory effect of Ang II on JGA renin, Ang II infusion stimulates renin protein expression in collecting ducts and maintains renin transcriptional levels in the medulla, which may contribute to the increased intrarenal Ang II levels in Ang II-dependent hypertension.