• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>PLoS Clinical Trials >Lack of Renoprotective Effect of Chronic Intravenous Angiotensin-(1-7) or Angiotensin-(2-10) in a Rat Model of Focal Segmental Glomerulosclerosis
【2h】

Lack of Renoprotective Effect of Chronic Intravenous Angiotensin-(1-7) or Angiotensin-(2-10) in a Rat Model of Focal Segmental Glomerulosclerosis

机译：在局灶性节段性肾小球硬化大鼠模型中，慢性静脉内血管紧张素-（1-7）或血管紧张素-（2-10）的肾保护作用缺乏

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Unopposed angiotensin (Ang) II-mediated cellular effects may lead to progressive glomerulosclerosis. While Ang-II can be locally generated in the kidneys, we previously showed that glomerular podocytes primarily convert Ang-I, the precursor of Ang-II, to Ang-(1-7) and Ang-(2-10), peptides that have been independently implicated in biological actions opposing those of Ang-II. Therefore, we hypothesized that Ang-(1-7) and Ang-(2-10) could be renoprotective in the fawn-hooded hypertensive rat, a model of focal segmental glomerulosclerosis. We evaluated the ability of 8–12 week-long intravenous administration of either Ang-(1-7) or Ang-(2-10) (100–400 ng/kg/min) to reduce glomerular injury in uni-nephrectomized fawn-hooded hypertensive rats, early or late in the disease. Vehicle-treated rats developed hypertension and lesions of focal segmental glomerulosclerosis. No reduction in glomerular damage was observed, as measured by either 24-hour urinary protein excretion or histological examination of glomerulosclerosis, upon Ang-(1-7) or Ang-(2-10) administration, regardless of peptide dose or disease stage. On the contrary, when given at 400 ng/kg/min, both peptides induced a further increase in systolic blood pressure. Content of Ang peptides was measured by parallel reaction monitoring in kidneys harvested at sacrifice. Exogenous administration of Ang-(1-7) and Ang-(2-10) did not lead to a significant increase in their corresponding intrarenal levels. However, the relative abundance of Ang-(1-7) with respect to Ang-II was increased in kidney homogenates of Ang-(1-7)-treated rats. We conclude that chronic intravenous administration of Ang-(1-7) or Ang-(2-10) does not ameliorate glomerular damage in a rat model of focal segmental glomerulosclerosis and may induce a further rise in blood pressure, potentially aggravating glomerular injury.
机译：无抵抗的血管紧张素（Ang）II介导的细胞作用可能导致进行性肾小球硬化。尽管Ang-II可以在肾脏中局部产生，但我们之前曾证明肾小球足细胞主要将Ang-II的前体Ang-I转换为Ang-（1-7）和Ang-（2-10）肽已经独立地涉及与Ang-II相反的生物作用。因此，我们假设Ang-（1-7）和Ang-（2-10）在小鹿型高血压大鼠（一种局灶节段性肾小球硬化模型）中可能具有肾脏保护作用。我们评估了为期8-12周的Ang-（1-7）或Ang-（2-10）（100-400 ng / kg / min）静脉输注减轻单肾切除小鹿的肾小球损伤的能力。在疾病的早期或晚期，戴头巾的高血压大鼠。媒介物治疗的大鼠发展为高血压和局灶性节段性肾小球硬化病变。 Ang-（1-7）或Ang-（2-10）给药后，无论肽剂量或疾病阶段如何，通过24小时尿蛋白排泄或肾小球硬化的组织学检查均未观察到肾小球损害的减少。相反，当以400 ng / kg / min的剂量给药时，两种肽均可引起收缩压进一步升高。通过平行反应监测在处死时收获的肾脏中测量Ang肽的含量。 Ang-（1-7）和Ang-（2-10）的外源给药并未导致其相应的肾内水平显着增加。然而，在Ang-（1-7）治疗的大鼠的肾脏匀浆中，Ang-（1-7）相对于Ang-II的相对丰度增加。我们得出的结论是，在大鼠局灶性节段性肾小球硬化模型中，长期静脉注射Ang-（1-7）或Ang-（2-10）并不能改善肾小球损害，并且可能导致血压进一步升高，并可能加重肾小球损伤。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号