The effect of aldose reductase inhibition and dietary protein restriction on renal function in experimental diabetes mellitus.
The effects of aldose reductase inhibition on renal function in hyperphagic diabetic rats were examined at 3 months. To prevent a high dietary protein intake from influencing renal function, protein intake in the diabetic animals was reduced to that of nondiabetic animals. To determine the influence of renal prostaglandins, clearance studies were performed before and after indomethacin infusion. Experiments were performed in uninephrectomized sorbinil-treated and -untreated streptozocin-diabetic and sorbinil-treated and -untreated control rats. Despite normalization of protein intake, the mean value of the insulin clearance (CIn, mL/min/100 g BW) was 83% greater in the untreated diabetic rats when compared to the untreated control rats (1.06 +/- 0.15 vs. 0.58 +/- 0.07; p less than 0.05). In contrast, the mean value of the CIn in the sorbinil-treated diabetic rats was significantly less than that in the untreated diabetic rats and only 38% greater than the mean value in the sorbinil-treated control rats (0.84 +/- 0.17 vs. 0.61 +/- 0.05; p less than 0.05). In a similar fashion, without sorbinil treatment the mean value of renal blood flow (RBF, mL/min/100 g BW) was greater in the diabetic than the control rats (6.58 +/- 2.03 vs. 3.70 +/- 0.68; p less than 0.05); whereas the mean values of RBF in the sorbinil-treated diabetic and control rats were not significantly different (4.75 +/- 0.73 vs. 4.17 +/- 0.64; NS). Indomethacin infusion failed to cause changes in the CIn and RBF in any group of animals.(ABSTRACT TRUNCATED AT 250 WORDS)
McCormack
A J
AJ
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill.
Hak
L J
LJ
Finn
W F
WF
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology* / Q000628:therapy; D004044:Dietary Proteins / Q000008:administration & dosage*; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D007213:Indomethacin / Q000627:therapeutic use; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
D004044:Dietary Proteins; D007093:Imidazoles; D048289:Imidazolidines; D000449:Aldehyde Reductase; C026411:sorbinil; D007213:Indomethacin