The objective of this proposal is to investigate the hypothesis that changes in renal perfusion pressure (RPP) may not be fully transmitted to the renal interstitium in hypertensive as compared with normotensive states, thus resulting in an attenuated pressure natriuresis and diuresis response. The acute and chronic relationship between sodium excretion and RPP is shifted to higher pressure values in many rat models of hypertension. The pressure natriuresis and diuresis response appears to be blunted in hypertension; however, the mechanism(s) responsible for it is not well understood. A method which allows for direct and continuous measurement of renal interstitial hydrostatic pressure (RIHP) in anesthetized rats was developed. A polyethylene (PE) matrix is implanted chronically in the kidney three weeks prior to RIHP measurement. On the day of the experiment, the PE-50 catheter is connected to a Micro Switch transducer and RIHP is measured and recorded directly and continuously in the anesthetized rat. RPP is manipulated by placing an inflatable servo- controlled cuff around the abdominal aorta above both renal arteries. The possibility that directly increasing RIHP in the SHR, by renal interstitial volume expansion (RIVE), might lead to normal acute pressure natriuresis and diuresis responses will be tested. The effect of chronic renal denervation on the relationship between RPP, RIHP, and sodium excretion will be determined in the SHR. In addition, the role of RIHP in the exaggerated natriuresis of SHR to acute saline volume expansion will be determined. Other hypertensive models that will be studies include Dahl salt-sensitive (S) rat, one kidney, one clip (1K1C), and two kidney, one clip (2K1C) hypertensive Sprauge-Dawley (SD) rats. In addition, the control rates of 1K1C (uninephrectomized SD rats) will show these relationships after a reduction in renal mass. The possible role of the renin- angiotensin system (RAS) in causing a shift in these relationships will also be assessed since 1K1C is a RAS-independent, while 2K1C is a RAS- dependent model of hypertension. The results of these experiments will help characterize the relationship between changes in RPP, RIHP, and sodium excretion in various forms of hypertension that have different pathogeneses. Comparisons of these relationships to those obtained before the development of hypertension, and from the appropriate normotensive control rats, will identify the possible role that RIHP may play int he mechanism of attenuated acute pressure natriuresis response in different rate models of hypertension.
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