Transplantation studies have indicated that an intrinsic renal abnormality may underlie the development of hypertension; however, identification of factors responsible for the """"""""resetting of the kidney in hypertension"""""""" has remained elusive. The proposed studies will evaluate the hypothesis that alterations in renal medullary hemodynamics play a significant role in the development and/or maintenance of hypertension in two genetic rat models (SHR and Dahl S) of the disease. The relationships between papillary blood flow (measured using a laser doppler flowmeter), vasa recta capillary pressure (measured using a servonull micropressure device) and renal perfusion pressure will be characterized and compared in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) as well as in hypertensive Dahl S and normotensive Dahl R rats. Similar experiments performed in young """"""""prehypertensive"""""""" SHR and WKY rats as well as in normotensive Dahl S rats maintained on a low salt diet should indicate whether changes in renal medullary hemodynamics exist early in the development of hypertension in these genetic models. Videomicroscopy techniques will be utilized to directly observe the microcirculation of the exposed papilla of normotensive and hypertensive rats in vivo in order to determine if changes in the number of perfused vasa recta capillaries might explain the abnormal papillary blood flow in hypertension. Experiments using electron microscopy techniques and morphometric analysis of Microfil silicon rubber casts of the medullary vasculature will evaluate the contribution of structural changes in the vasculature of juxtamedullary nephrons to the altered medullary hemodynamics in hypertension. Finally, the influence of angiotensin II and renal prostanoids on the regulation of papillary blood flow in hypertensive and normotensive rats will be compared to determine the involvement of changes in the control of medullary vascular resistance by these autocoids in the development of hypertension. The proposed studies should further the understanding of the regulation of the renal medullary circulation and the influence of medullary blood flow on the pressure-diuresis relationship and the control of arterial pressure. These studies will provide the first detailed comparative information regarding hemodynamics and morphology in the vasa recta circulation of normotensive and genetically hypertensive rats. Overall, this research will furnish needed information to better understand the role of the kidney in long term control of arterial pressure.
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