Although it is well known that diabetes, renal ablation and high protein intake increase glomerular filtration rate (GFR) and alter glomerular hemodynamics, it is not clear why these changes occur. Experiments described in this proposal will involve use of in vivo micropuncture and microperfusion techniques to examine the possibility that states of glomerular hyperfiltration depend on an intrinsic failure of the tubuloglomerular feedback (TGF) system to restrain increments in GFR. One series of experiments will examine TGF function in rats made diabetic by injection of streptozotocin. A similar series of experiments will examine TGF function in rats subjected to removal of 25%, 50%, 75% or 90% of renal mass. A last series of experiments will examine whether administration of adenosine agonists and dipyridamole, agents known to increase TGF action and reduce GFR in conditions not involving hyperfiltration, will have the same actions during hyperfiltration due to diabetes, renal ablation and high protein intake. It has been suggested that glomerular hyperfiltration can cause progressive loss of renal function in diabetes and patients with reduced renal mass. Since there is intense clinical interest in this possibility, it is particularly important to understand what factors cause hyperfiltration. It is hoped that information from these studies will further the understanding of the hyperfiltration process and provide strategies for the alleviation of its possible adverse consequences.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK038968-01
Application #
3238585
Study Section
General Medicine B Study Section (GMB)
Project Start
1987-08-01
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Salmond, R; Seney Jr, F D (1991) Reset tubuloglomerular feedback permits and sustains glomerular hyperfunction after extensive renal ablation. Am J Physiol 260:F395-401
Seikaly, M G; Arant Jr, B S; Seney Jr, F D (1990) Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest 86:1352-7
Seney Jr, F D; Marver, D (1989) Protein intake and cation transport in the loop of Henle. J Lab Clin Med 114:587-94