Department of Research, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.
Pediatr Nephrol. 2010 Dec;25(12):2449-57. doi: 10.1007/s00467-010-1621-z. Epub 2010 Aug 27.
Hypertension is a well-recognized complication of autosomal recessive polycystic kidney disease (ARPKD). The renin-angiotensin system (RAS) is a key regulator of blood pressure; however, data on the RAS in ARPKD are limited and conflicting, showing both up- and down-regulation. In the current study, we characterized intrarenal and systemic RAS activation in relationship to hypertension and progressive cystic kidney disease in the ARPKD orthologous polycystic kidney (PCK) rat. Clinical and histological measures of kidney disease, kidney RAS gene expression by quantitative real-time PCR, angiotensin II (Ang II) immunohistochemistry, and systemic Ang I and II levels were assessed in 2-, 4-, and 6-month-old cystic PCK and age-matched normal rats. PCK rats developed hypertension and progressive cystic kidney disease without significant worsening of renal function or relative kidney size. Intrarenal renin, ACE and Ang II expression was increased significantly in cystic kidneys; angiotensinogen and Ang II Type I receptor were unchanged. Systemic Ang I and II levels did not differ. This study demonstrates that intrarenal, but not systemic, RAS activation is a prominent feature of ARPKD. These findings help reconcile previous conflicting reports and suggest that intrarenal renin and ACE gene upregulation may represent a novel mechanism for hypertension development or exacerbation in ARPKD.
高血压是常染色体隐性多囊肾病（ARPKD）的一种公认并发症。肾素-血管紧张素系统（RAS）是血压的关键调节系统；然而，ARPKD 中 RAS 的数据有限且相互矛盾，表现为上调和下调。在本研究中，我们描述了与高血压和进行性囊性肾病相关的肾内和全身 RAS 激活在 ARPKD 同源性多囊肾病（PCK）大鼠中的作用。通过定量实时 PCR、血管紧张素 II（Ang II）免疫组织化学和系统 Ang I 和 II 水平评估了 2、4 和 6 月龄囊性 PCK 和年龄匹配的正常大鼠的临床和组织学肾脏病指标、肾脏 RAS 基因表达、Ang II 免疫组织化学和系统 Ang I 和 II 水平。PCK 大鼠出现高血压和进行性囊性肾病，但肾功能或相对肾大小无明显恶化。囊性肾脏中肾素、ACE 和 Ang II 的表达显著增加；血管紧张素原和 Ang II 型 1 受体不变。系统 Ang I 和 II 水平没有差异。本研究表明，肾内而非全身 RAS 激活是 ARPKD 的一个显著特征。这些发现有助于调和以前相互矛盾的报告，并表明肾内肾素和 ACE 基因上调可能是 ARPKD 中高血压发展或加重的一种新机制。
