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

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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.