It is the purpose of the proposed research to determine the mechanism of the renal hyperemia which develops shortly after the onset of diabetes mellitus. It is established that in juvenile-onset IDDM and in animals with experimental diabetes, renal blood flow and glomerular filtration rate increase to supernormal levels within a short period after onset of the disease. Identification of the mechanism for the renal hyperermia is of major importance, as increased hydraulic pressure and flow rates within blood vessels and glomerular capillaries could be responsible for progressive renal damage, which occurs in diabetes. In the proposed experiments, rats with streptozotocin-induced diabetes will be studied by micropuncture techniques within 1 week after onset of diabetes. It has been shown that renal hyperemia is present at this time. Single nephron glomerular capillary pressure, plasma flow, filtration rate and filtration fraction will be measured in the left kidney during specific experimental maneuvers. These measurements will be made during infusion of various substances into the left renal artery. Whole kidney blood flow and filtration will be measured separately for each kidney, using the right kidney as the control organ. The specific systems involved in regulation of renal hemodynamics will be examined: renal-angiotensin system; renal prostaglandin system; renal kallikrein-kinin system; and renal catecholamine system. The experimental designs take into account the complex interactions among these four hormones systems involved in regulation of renal hemodynamics. In addition, the functioning of the tubuloglomerular feedback mechanism will be studied in early diabetic rats, by microperfusion of lth distal tubule and proximal tubular pressure measurements. The response to calcium, magnesium, potassium and glucose infused into the distal tubule will be examined. Finally, micropuncture experiments will be carried out in rats with combined spontaneous hypertension and streptozotocin diabetes to determine the cause of accelerated renal damage. The long-term objectives are to determine the mechanism of renal hyperemia in diabetes and then to design therapeutic interventions which would prevent the hyperemia. We would evaluate whether preventing renal hyperemia aborts progressive renal damage in long-term diabetes mellitus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK032469-04
Application #
3230889
Study Section
General Medicine B Study Section (GMB)
Project Start
1983-08-01
Project End
1987-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10467