Aldose reductase inhibition and glomerular abnormalities in diabetic rats.
We examined the effects of aldose reductase inhibition (ARI) on glomerular filtration rate (GFR), albuminuria, and kidney histology in partially insulin-treated streptozocin-induced diabetic (STZ-D) rats. After 1 mo of diabetes, GFR was elevated over control values in the STZ-D rats but was not affected by treatment with statil (an aldose reductase inhibitor). In another set of rats maintained for 7 mo, albuminuria was significantly increased in the diabetic rats from 2 mo on but was also not affected by statil treatment. Similarly, histological glomerular damage and diabetes-induced kidney hypertrophy were also greater in diabetic animals but were not altered by statil treatment. The frequency of diabetic cataracts was reduced by statil, and erythrocyte and kidney sorbitol levels were normalized, confirming the efficacy of ARI. Thus, inhibition of the aldose reductase pathway with statil does not ameliorate the hemodynamic, proteinuric, histological, or growth abnormalities in this model of diabetic nephropathy.
Daniels
B S
BS
Department of Medicine, University of Minnesota, Minneapolis 55455.
Hostetter
T H
TH
D000419:Albuminuria / Q000503:physiopathology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007678:Kidney Glomerulus / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010793:Phthalazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D013997:Time Factors
D010793:Phthalazines; C042829:ponalrestat; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase