Project: Research project

Project Details


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.
Effective start/end date6/1/797/31/09


  • National Heart, Lung, and Blood Institute: $390,059.00


  • Medicine(all)


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