The proposed studies will determine if the renal medulla plays an important role in determining the long-term level of arterial blood pressure. We will chronically reduce papillary blood flow to see if this leads to hypertension and chronically elevate papillary flow to see if this leads to hypotension. Two new techniques were necessary and are used for these studies. One, implanted medullary interstitial catheters to target delivery of substances into the renal medulla, acutely and chronically. The other, acute and chronically implanted optical fibers in the renal cortex, outer and inner medulla for measurement of changes in regional blood flow using laser-Doppler flowmetry. These techniques have been designed to be performed in conscious rats and at this time can be used reliably for periods exceeding 3 weeks. One series of studies is designed to determine the acute effects of renal medullary interstitial infusions of vasoconstrictors and dilators which alter papillary blood flow will produce chronic alterations of arterial pressure. A third series of studies will determine if chronic medullary interstitial infusion of compounds that increase papillary blood flow in SHR can reset the pressure-natriuretic relationship and normalize arterial pressure. Positive findings would support the concept that subtle changes in medullary function may precede global changes in renal function and may be an important initiating element in the etiology of hypertension.
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