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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL016496-18
Application #
3335216
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1979-06-01
Project End
1994-05-31
Budget Start
1992-06-01
Budget End
1993-05-31
Support Year
18
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Lavi, Ronit; Zhu, Xiang-Yang; Chade, Alejandro R et al. (2010) Simvastatin decreases endothelial progenitor cell apoptosis in the kidney of hypertensive hypercholesterolemic pigs. Arterioscler Thromb Vasc Biol 30:976-83
Gomez, Sabas I; Warner, Lizette; Haas, John A et al. (2009) Increased hypoxia and reduced renal tubular response to furosemide detected by BOLD magnetic resonance imaging in swine renovascular hypertension. Am J Physiol Renal Physiol 297:F981-6
Textor, Stephen C (2009) Current approaches to renovascular hypertension. Med Clin North Am 93:717-32, Table of Contents
Warner, Lizette; Gomez, Sabas I; Bolterman, Rodney et al. (2009) Regional decreases in renal oxygenation during graded acute renal arterial stenosis: a case for renal ischemia. Am J Physiol Regul Integr Comp Physiol 296:R67-71
Reisin, Efrain; Jack, Avanelle V (2009) Obesity and hypertension: mechanisms, cardio-renal consequences, and therapeutic approaches. Med Clin North Am 93:733-51
Textor, Stephen C; Glockner, James F; Lerman, Lilach O et al. (2008) The use of magnetic resonance to evaluate tissue oxygenation in renal artery stenosis. J Am Soc Nephrol 19:780-8
Gomez, S I; Strick, D M; Romero, J C (2008) Role of nitric oxide and prostaglandin in the maintenance of cortical and renal medullary blood flow. Braz J Med Biol Res 41:170-5
Textor, Stephen C (2008) Atherosclerotic renal artery stenosis: overtreated but underrated? J Am Soc Nephrol 19:656-9
Bentley, Michael D; Jorgensen, Steven M; Lerman, Lilach O et al. (2007) Visualization of three-dimensional nephron structure with microcomputed tomography. Anat Rec (Hoboken) 290:277-83

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