RENAL HUMORAL FACTORS IN RENAL FUNCTION AND HYPERTENSION

当前提案的目标是确定如何

The objective of the current proposal is to determine how alterations in renal perfusion pressure (RPP) can modify urinary sodium excretion (UNa) without changes in renal blood flow (RBF) or glomerular filtration rate. The mechanisms responsible for this pressure-related natriuresis have remained unknown despite their attributed importance in the regulation of blood pressure. From experimental data reported by us and others, we have proposed a hypothetical sequence of events by which UNa is altered in proportion to changes in RPP. According to this hypothesis, changes in RPP produce inversely related changes in renin release and thereby in the intrarenal formation of angiotensin II (Ang II) Ang II modulates blood flow to the renal medulla by controlling the vascular tone of the vasa recta. Changes in medullary blood flow induce parallel changes in medullary volume and in renal interstitial pressure altering the production of prostaglandin E2 (PGE2) from renal interstitial cells. Sodium reabsorption in lace proximal tubules or thick ascending limbs may be modulated by PGE2. This proposal will test this sequence of events 1) in dogs using conventional techniques for measuring alterations in these parameters as RPP is decreased within and below the range of RBF autoregulation. Changes in cortical and medullary flow and volume will be measured using a fast x-ray computerized tomographic system. 2) The interactions between the pressure related events and other factors influencing prostaglandin synthesis in the renal medulla. (i.e. osmotic pressure, 02 tension, and urea concentration) will be investigated in canine medullary slices 3) The influence of RPP-dependent physical factors such as wall tension and shear stress, on the release of endothelia derived relaxing factors (EDRF) and prostacyclin (PGI2) will be studied in canine renal arteries placed in chambers where each physical factor can be independently controlled. 4) Studies will also be undertaken to determine how EDRF and PGI2 produced in renal arterial segments modulate the release of renin from renal cortical slices or juxtaglomerular cell preparations. These studies will elucidate the mechanisms by which the kidney regulates volume and, thereby, blood pressure.