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ANGIOTENSIN RECEPTOR GENES AND BLOOD PRESSURE REGULATION

ANGIOTENSIN RECEPTOR GENES AND BLOOD PRESSURE REGULATION
血管紧张素受体基因和血压调节
批准号:
2857874
负责人:
THOMAS M COFFMAN
金额:
$20.45万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-01-01 至 1999-12-31

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中文摘要
翻译
描述:肾素-血管紧张素系统 (RAS) 在 调节血压和钠平衡,这些作用是介导的 通过 I 型血管紧张素 (AT1) 受体。 RAS 在肾脏中发挥作用 通过可能影响钠处理的三种不同途径:(1) 肾小球循环水平的血流动力学效应由 AT1受体对肾脉管系统(2)对钠转运的直接影响 由近端肾小管上皮细胞上表达的AT1受体调节 (3)醛固酮对远端肾单位钠重吸收的调节 在肾上腺皮质中的AT1受体的控制下。 在老鼠身上,有两个 单独的AT1受体基因控制这些功能:AgtrlA和AgtrlB。 使用小鼠模型,其中这些AT1受体基因的表达已经被 使用基因靶向进行特别改变,建议确定 AT1血管紧张素受体基因通过调节血压的作用 具体目标如下: 具体目标 I:定义 ATlA 受体在肾脏适应饮食钠摄入量改变中的作用 假设肾脏钠处理异常会导致钠 将研究 AgtrlA (-/-) 小鼠的依赖性血压变化。 具体目标 II:检查肾脏 AgtrlA 表达在 血压的调节,肾 ATlA 受体的贡献 肾交叉移植实验中血压的控制 将确定 AgtrlA (/) 和 AgtrlA (-/-) 小鼠之间的关系。 具体目标 III: 确定肾上皮作用的贡献 血管紧张素 II 对血压和钠稳态转基因小鼠的影响 肾脏中 ATlA 受体仅在肾上皮细胞上表达 近端小管将发育。 具体目标四:确定角色 AT1B 受体在 AgtrlA (-/-) 小鼠血压调节中的作用,RAS 将研究膳食钠的调节和血压反应 当 AT1B 受体受到抑制或缺失时。 具体目标 V:定义 AgtrlB 基因对血压调节的贡献 将研究 AgtrlB 基因的靶向破坏。
英文摘要
DESCRIPTION: The renin-angiotensin system (RAS) plays a critical role in regulating blood pressure and sodium balance and these actions are mediated through angiotensin type I (AT1) receptors. In the kidney, the RAS acts through three distinct pathways that may influence sodium handling: (1) hemodynamic effects at the level of the glomerular circulation mediated by ATl receptors on renal vasculature (2) direct effects on sodium transport modulated by ATl receptors expressed on proximal tubular epithelial cells (3) regulation of sodium reabsorption in the distal nephron by aldosterone under the control of ATl receptors in the adrenal cortex. In the mouse, two separate ATl receptor genes control these functions: AgtrlA and AgtrlB. Using mouse models in which expression of these ATl receptor genes has been specifically altered using gene targeting, it is proposed to determine the role of ATl angiotensin receptor genes in regulating blood pressure through the following specific aims: Specific Aim I: To define the role of the ATlA receptor in renal adaptation to altered dietary sodium intake, the hypothesis that abnormal renal sodium handling contributes to sodium dependent blood pressure changes in the AgtrlA (-/-) mice will be studied. Specific Aim II: To examine the role of renal AgtrlA expression in the regulation of blood pressure, the contribution of renal ATlA receptors to the control of blood pressure in renal cross transplantation experiments between AgtrlA (+/+) and AgtrlA (-/-) mice will be determined. Specific Aim III: To determine the contribution of renal epithelial actions of angiotensin II to blood pressure and sodium homeostasis transgenic mice that express the ATlA receptor in the kidney only on epithelial cells in the proximal tubule will be developed. Specific Aim IV: To determine the role of AT1B receptors in blood pressure regulation in AgtrlA (-/-) mice, RAS regulation by dietary sodium, and blood pressure responses will be studied when AT1B receptors are inhibited or absent. Specific Aim V: To define the contribution of the AgtrlB gene to blood pressure regulation, mice with targeted disruption of the AgtrlB gene will be studied.
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Paracrine Control of Blood Pressure by Renal Intercalated Cells
  • 批准号:
    9070607
  • 项目类别:
  • 资助金额:
    $35.78万
  • 财政年份:
    2015
  • 负责人:
    THOMAS M COFFMAN
  • 依托单位:
Administrative Core
  • 批准号:
    8433280
  • 项目类别:
  • 资助金额:
    $18.05万
  • 财政年份:
    2012
  • 负责人:
    THOMAS M COFFMAN
  • 依托单位:
George M. O'Brien Kidney Research Core Centers
  • 批准号:
    8385010
  • 项目类别:
  • 资助金额:
    $115.72万
  • 财政年份:
    2012
  • 负责人:
    THOMAS M COFFMAN
  • 依托单位:
George M. O'Brien Kidney Research Core Centers
  • 批准号:
    8912150
  • 项目类别:
  • 资助金额:
    $3.02万
  • 财政年份:
    2012
  • 负责人:
    THOMAS M COFFMAN
  • 依托单位:
海外基金