Galactose feeding causes glomerular hyperperfusion: prevention by aldose reductase inhibition.
Experimental dietary galactosemia is known to result in accumulation of the polyol, galactitol, via the aldose reductase metabolic pathway in a variety of tissues, including renal glomeruli. Because increased polyol accumulation also occurs in insulin-dependent diabetes mellitus (IDDM), in which marked renal glomerular hyperperfusion occurs, we have studied glomerular hemodynamics in rats with experimental galactosemia. Insulin deficiency and its accompanying metabolic disorders are not present in this experimental model. In additional groups of animals, aldose reductase inhibitors, either sorbinil or tolrestat, were added to the galactose diet. In all, five groups of rats were studied: regular diet, 50% galactose diet, regular diet plus sorbinil, 50% galactose diet plus sorbinil, and 50% galactose plus tolrestat. The diets were comparable in protein and salt, and the rats were pair fed. Micropuncture and whole kidney clearance measurements were carried out after 10-14 days on these diets. Compared with rats fed the regular diet, those fed with 50% galactose diet had significantly higher glomerular filtration rates, renal plasma flow, single-nephron glomerular filtration rates, and plasma flow (QA), whereas afferent vascular resistance (RA) was decreased. Addition of sorbinil or tolrestat to the high-galactose diet not only prevented renal hyperperfusion but RA and single-nephron filtration fraction (SNFF) were higher than in normal rats, and QA was lower. In addition, sorbinil administration to rats on the control diet caused significant decreases in single-nephron blood flow and the ultrafiltration coefficient and a rise in SNFF.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Medicine, Montefiore Medical Center, Bronx, New York.
Coco
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Aynedjian
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D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D005690:Galactose / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008433:Mathematics; D008962:Models, Theoretical; D009281:Naphthalenes / Q000494:pharmacology*; D009399:Nephrons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D048289:Imidazolidines; D009281:Naphthalenes; C040550:tolrestat; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil; D005690:Galactose