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Abstract
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 normalizaiton of protein intake, the mean value of the inulin 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 < 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 < 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 < 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. These data provide evidence that renal hemodynamic abnormalities occur in the diabetic kidney which are not a result of an increase in dietary protein intake or stimulation of renal prostaglandins. Furthermore, these data support the notion that increased polyol pathway activity is an important component of the renal hemodynamic abnormalities in the diabetic kidney.