The aim of the proposed project is to test the hypothesis that rats with genetic hypertension (SHR) and normotensive rats have differences in the dynamic characteristics of their tubuloglomerular feedback systems (TGF). TGF is an intrarenal control system that is important for the regulation of renal blood flow and the glomerular filtration rate, and therefore for salt and water excretion. We hypothesize that this difference leads to a change in the renal response to spontaneously occurring fluctuations in the arterial pressure, and therefore to a difference in the overall renal excretory function, which could be of significance in the development of high blood pressure. The hypothesis is based on the idea that the development of hypertension is always associated with a change in kidney function, especially the ability of the kidney to excrete salt in response to changes in the blood pressure. Earlier work has shown a difference in the dynamic properties of the TGF system present with hypertension. For example the hydrostatic pressure in the proximal tubule of the rat kidney oscillates with a well defined frequency around 30-50 mHz (2-3 cycles/min) in normotensive rats. These regular oscillations are not found in hypertensive rats. Instead the proximal pressure shows an irregular type of fluctuation, suggestive of a chaotic process. Since several studies have indicated that these oscillations are the result of the operation of the TGF system, the disappearance of the oscillatory pattern indicates that there are significant differences in the dynamic properties between the normal and the hypertensive rat strains. We propose to identify and quantify these differences in the TGF system experimentally, and to test the significance of these differences through computer simulation. Further, it has been shown that individual nephrons interact with each other. We therefore also propose to study, both experimentally and through computer simulation, the impact of this interaction on renal function. Using an integrative approach the proposed study will combine newly obtained data with previous data regarding both structure and function of the TGF system. Identifying differences in the dynamical characteristics in kidney function between normotensive and hypertensive rats may lead to a better understanding of the role of the kidney in hypertension, and possibly to new treatment principles.
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