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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 采用显微CT/数字减影分析。血液流动的综合控制对于调节肾脏的几乎所有功能至关重要。例如，肾皮质血流的改变会影响肾小球滤过率，而髓质血流的控制则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流动力学功能，这些系统的影响可能在肾脏的不同区域有所不同。在这一点上，血管紧张素II是一种有效的血管收缩药，作用于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(PGE2)是一种肾脏血管扩张剂，可以促进钠尿，并可能缓冲肾脏血管紧张素II的血管收缩效应。我们已经开发了转基因小鼠品系，作为检查这些系统的生理行为的工具。在一个品系中，血管紧张素II的主要血管收缩受体已经从血管平滑肌细胞中特异性地删除；另一个品系缺乏PGE2的主要合成酶mPGES1。在与CIVM研究人员的合作下，我们建议确定这些突变对肾血流控制的影响。成功完成这些研究将需要开发和表征测量小鼠肾脏局部血流的新方法。这些方法将用于确定血管紧张素II和前列腺素E_2对肾脏血流动力学的分子控制。

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.