ANGIOTENSIN RECEPTORS/PROSTAGLANDIN E2-REGIONAL BLOOD FLOW IN MOUSE KIDNEY

血管紧张素受体/前列腺素 E2 小鼠肾脏区域血流

• 批准号: 7726151
• 负责人: THOMAS M COFFMAN
• 金额: $ 0.65万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726151
• 关键词: Affect; Angiotensin II; Angiotensin II Receptor; Angiotensin Receptor; Blood Vessels; Blood flow; Buffers; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Development; Dinoprostone; Funding; Glomerular Filtration Rate; Grant; Hormones; Hydrostatic Pressure; Institution; Kidney; Liquid substance; Measures; Methods; Molecular; Mus; Mutation; Natriuresis; Physiological; Regional Blood Flow; Renal Blood Flow; Renal function; Research; Research Personnel; Resources; Smooth Muscle Myocytes; Source; System; United States National Institutes of Health; Vasoconstrictor Agents; Vasodilator Agents; digital; hemodynamics; kidney cortex; mouse membrane-associated prostaglandin E synthase; novel strategies; solute; synthetic enzyme; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Using micro-CT/digital subtraction analysis. Integrated control of blood flow is critical to regulating virtually all of the functions of the kidney. For example, alteration of blood flow in the renal cortex affects glomerular filtration rate, whereas control of blood flow in the medulla impacts fluid and solute reabsorption. Several hormone systems are involved in coordinating these hemodynamic functions and the impact of these systems may vary in different regions of the kidney. In this regard, angiotensin II is a potent vasoconstrictor acting to increase glomerular hydrostatic pressure while reducing medullary blood flow. By contrast, prostaglandin E2 (PGE2) is a renal vasodilator that promotes natriuresis and likely buffers the vasoconstrictor effects of angiotensin II in the kidney. We have developed genetically modified mouse lines as tools for examining the physiological actions of these systems. In one line, the major vasoconstrictor receptor for angiotensin II has been specifically deleted from vascular smooth muscle cells; another line is deficient in the major synthetic enzyme for PGE2, mPGES1. In collaboration with CIVM investigators, we propose to determine the consequences of these mutations on control of renal blood flow. Successful completion of these studies will require development and characterization of novel approaches for measuring regional blood flow in the mouse kidney. These methods will be used to define the molecular control of renal hemodynamics by angiotensin II and PGE2.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 使用Micro-CT/数字减法分析。血流的综合控制对于调节几乎所有肾脏功能至关重要。 例如，肾皮质中血流的改变会影响肾小球滤过率，而延髓中血流的控制会影响液体和溶质的重吸收。 几种激素系统参与协调这些血液动力学功能，这些系统的影响在肾脏的不同区域可能会有所不同。 在这方面，血管紧张素II是一种有效的血管收缩剂，可在减少髓样血流的同时增加肾小球静水压力。 相比之下，前列腺素E2（PGE2）是一种肾血管扩张剂，可促进纳特里雷SIS，并可能缓冲血管紧张素II在肾脏中的血管收缩作用。 我们已经开发了转基因的小鼠线，作为检查这些系统生理作用的工具。 在一条线中，血管紧张素II的主要血管收缩受体已被特异性从血管平滑肌细胞中删除。另一个线路缺乏PGE2，MPGES1的主要合成酶。 我们建议与CIVM研究人员合作，确定这些突变对控制肾脏血流的后果。 这些研究的成功完成将需要开发和表征用于测量小鼠肾脏区域血流的新方法。 这些方法将用于定义血管紧张素II和PGE2对肾血液动力学的分子控制。