We will focus upon mechanisms contributing to the regulation of glomerular ultrafiltration and processes which link renal tubular reabsorption to glomerular function. Studies in the Munich-Wistar rat will involve micropuncture evaluation of glomerular hemodynamics and glomerular hemodynamics at the single nephron level and, evaluation of tubuloglomerular feedback activity, a process which links tubular reabsorption to the filtration process, using microperfusion techniques. Other studies will involve clearance evaluations in the chronically catheterized rat, evaluation of glomerular angiotensin II receptors, measurement of prostaglandins in urinary and tubular fluid and in isolated glomeruli by radioimmunoassay and, in certain studies, the use of glomerular mesangial cells in culture. First, we will define the glomerular mechanisms and limiting barriers contributing to a reduction in the glomerular ultrafiltration coefficient (LPA) using a) cationic molecules such as hexadimethrine (HDM) which alter the size and charge selective properties of the glomerular basement membrane, b) agents such as chlorpromazine which prevent epithelial cell changes after administration of anti-Fx1A antibody, and c) specific antibodies directed to glomerular mesangial cells and the effects of mesangiolysis and mesangial proliferation on the LPA response to AII. Second, the mechanism of changes in and role of tubulo-glomerular feedback activity in 1) acute volume expansion, 2) 6-24 hours of nephron obstruction and the role of enhanced feedback sensitivity, 3) the adaptation to reduction in renal mass and the role of renal prostanoids and cyclosporine, and 4) the role of feedback activity in a single nephron model of uranyl-nitrate induced acute renal failure. Studies will evaluate all determinants of glomerular ultrafiltration in a single nephron unit. Third, studies will examine the functional alteration in glomerular AII receptors, intrarenal AI and AII generation, response to infused AII and autoregulation of SNGFR in chronic NaCl depleted rats with and without angiotensin and/or prostaglandin blockade. Fourth, we propose to further examine the role of major alterations in peritubular capillary oncotic pressure upon absolute proximal tubular reabsorption (APR) in an experimental model of nephrotic syndrome and a model in which the active component of APR has been markedly decreased by other physiologic maneuvers, to determine if these changes in physical factors are capable of increasing APR.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK028602-18
Application #
3228939
Study Section
General Medicine B Study Section (GMB)
Project Start
1982-02-01
Project End
1992-01-31
Budget Start
1990-05-01
Budget End
1991-01-31
Support Year
18
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Blantz, Roland C; Steiner, Robert W (2015) Benign hyperfiltration after living kidney donation. J Clin Invest 125:972-4
Blantz, Roland C; Singh, Prabhleen (2014) Glomerular and tubular function in the diabetic kidney. Adv Chronic Kidney Dis 21:297-303
Declèves, Anne-Emilie; Sharma, Kumar; Satriano, Joseph (2014) Beneficial Effects of AMP-Activated Protein Kinase Agonists in Kidney Ischemia-Reperfusion: Autophagy and Cellular Stress Markers. Nephron Exp Nephrol :
Blantz, Roland C (2014) Phenotypic characteristics of diabetic kidney involvement. Kidney Int 86:7-9
Rieg, Timo; Tang, Tong; Uchida, Shinichi et al. (2013) Adenylyl cyclase 6 enhances NKCC2 expression and mediates vasopressin-induced phosphorylation of NKCC2 and NCC. Am J Pathol 182:96-106
Satriano, Joseph; Sharma, Kumar; Blantz, Roland C et al. (2013) Induction of AMPK activity corrects early pathophysiological alterations in the subtotal nephrectomy model of chronic kidney disease. Am J Physiol Renal Physiol 305:F727-33
Hansell, Peter; Welch, William J; Blantz, Roland C et al. (2013) Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension. Clin Exp Pharmacol Physiol 40:123-37
Vallon, Volker; Rose, Michael; Gerasimova, Maria et al. (2013) Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus. Am J Physiol Renal Physiol 304:F156-67
Satriano, Joseph; Sharma, Kumar (2013) Autophagy and metabolic changes in obesity-related chronic kidney disease. Nephrol Dial Transplant 28 Suppl 4:iv29-36
Vallon, Volker; Stockand, James; Rieg, Timo (2012) P2Y receptors and kidney function. Wiley Interdiscip Rev Membr Transp Signal 1:731-742

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