Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats.
The effects of aldose reductase inhibition on kidney function were studied in rats with streptozotocin-induced diabetes mellitus. Diabetic rats were fed sorbinil (20 and 50 mg/kg) by daily gastric gavage and were compared with untreated diabetic rats and normal rats. The rats were under daily supervision with regard to blood glucose control, insulin administration and body weight. The aim was to promote continuous body growth and to maintain the blood glucose concentration at around 22 mmol/l without large day-to-day fluctuations. The renal functional changes observed in this well-established diabetic model closely resembled those reported in human Type 1 (insulin-dependent) diabetes mellitus. Sorbinil treatment completely prevented renal cortical sorbital accumulation, but did not abolish kidney enlargement or the increase in ultrafiltration pressure and glomerular filtration rate. Albumin excretion was increased to the same extent in the sorbinil-treated and in the untreated diabetic rats. We conclude that increased metabolism of glucose to sorbitol does not cause the hyperfiltration in rats with streptozotocin-induced diabetes.
Körner
A
A
Department of Pediatrics, St. Göran's Children's Hospital, Stockholm, Sweden.
Celsi
G
G
Eklöf
A C
AC
Linné
T
T
Persson
B
B
Aperia
A
A
D000419:Albuminuria; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013012:Sorbitol / Q000378:metabolism; D014462:Ultrafiltration
D007093:Imidazoles; D048289:Imidazolidines; D013012:Sorbitol; D000449:Aldehyde Reductase; C026411:sorbinil