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.

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 采用显微CT/数字减影分析。血流量的综合控制对于调节肾脏的几乎所有功能至关重要。 例如，肾皮质中血流的改变影响肾小球滤过率，而髓质中血流的控制影响液体和溶质重吸收。 几种激素系统参与协调这些血液动力学功能，这些系统的影响可能在肾脏的不同区域有所不同。 在这方面，血管紧张素II是一种有效的血管收缩剂，作用是增加肾小球静水压力，同时减少髓质血流量。 相比之下，前列腺素E2（PGE 2）是一种肾血管扩张剂，可促进尿钠排泄，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小鼠品系作为研究这些系统的生理作用的工具。 在一个细胞系中，血管紧张素II的主要血管收缩受体已从血管平滑肌细胞中特异性缺失;另一个细胞系缺乏PGE 2的主要合成酶mPGES 1。 与CIVM研究人员合作，我们建议确定这些突变对肾血流控制的后果。 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中局部血流量的新方法。 这些方法将用于确定血管紧张素II和PGE 2对肾血流动力学的分子控制。