The overall objective of the research plan is to understand the mechanisms underlying long-term control of blood pressure in angiotensin type IA (AT1A) receptor deficient mice. Our working hypothesis is that angiotensin II directly contributes to the long-term regulation of blood pressure through it's effects on proximal tubule sodium reabsorption. To test this hypothesis we will define the how the lack of the AT1A receptor affects proximal tubular sodium reabsorption and medullary blood flow in sodium restricted and supplemented states in AT1A receptor deficient mice. To determine the contribution of the proximal tubule to long-term blood pressure control and sodium reabsorption, a mouse model lacking AT1A receptor exclusively in the proximal tubule will be generated. By generating a new mouse model in which the AT1A receptor can be ablated only in the proximal tubule at a specific time using modern molecular techniques, the proposed experiments should selectively integrate the intrarenal proximal tubule sodium handling and medullary blood flow contributions to blood pressure control. The candidate is committed to the development of a career in academic nephrology with a focus on basic science research in kidney disease. She has demonstrated her potential as a basic science investigator during the elective 3 years spent in the laboratory. The Research Career Award would allow her the opportunity to learn mouse renal physiology, and modern molecular techniques including homologous recombination. The long-term career goal is to utilize knowledge discovered in the basic science experiments and translate this knowledge into applicable clinical therapies in hypertensive kidney disease. The University of Virginia School has a long track record in training independent basic investigators. The mentor, Dr. R. Ariel Gomez, has a productive record in both research and research training for over fifteen years. The available graduate-level courses and multiple research support centers will provide opportunities for both formal and informal training. The Nephrology Divisions will ensure protected time for her research and didactic work.
