Sorbinil prevents glomerular hyperperfusion in diabetic rats.
The role of polyol pathway metabolism in glomerular hyperperfusion of insulin-dependent diabetes mellitus (IDDM) was studied in rats. Streptozotocin-induced diabetic rats were fed the aldose reductase inhibitor, sorbinil (8 mg/day). Untreated diabetic rats and normal rats served as controls. All groups were fed the same diet, rationed to 20 g/day. Micropuncture, plasma renin activity (PRA), and glomerular angiotensin II (ANG II)-receptor measurements were made 7-15 days after streptozotocin injection. Untreated diabetic rats had higher than normal single-nephron filtration rate (SNGFR), plasma flow (QA), and blood flow (SNBF), and reduced afferent resistance. Glomerular ANG II-receptor sites were markedly decreased. In diabetic rats fed sorbinil SNGFR, QA, and SNBF were all lower than in untreated diabetic rats, and indistinguishable from values in normal rats. However, single-nephron filtration fraction (SNFF) rose above normal. PRA, glomerular ANG II receptors, and blood glucose were not affected by sorbinil. In normal rats fed sorbinil, SNGFR, QA, and SNBF were not significantly different than in normal rats. Our observations are consistent with the view that polyol pathway metabolism plays a role in glomerular hyperperfusion in IDDM. Inhibition of aldose reductase increased vascular smooth muscle tone at pre- and probably postglomerular sites.
Bank
N
N
Department of Medicine, Montefiore Medical Center, Bronx.
Mower
P
P
Aynedjian
H S
HS
Wilkes
B M
BM
Silverman
S
S
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008433:Mathematics; D008962:Models, Theoretical; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D048289:Imidazolidines; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil