TIME-DEPENDENT ASPECTS OF OSMOLYTE CHANGES IN RAT-KIDNEY, URINE, BLOOD AND LENS WITH SORBINIL AND GALACTOSE FEEDING

Sorbitol plus myo-inositol, betaine and glycerophosphorylcholine (GPC) are cellular osmolytes in the mammalian renal medulla. Galactosemia a nd hyperglycemia can cause excessive levels of galactitol or sorbitol in several organs via aldose reductase (AR) catalysis. AR inhibitors c an reduce these polyols. To examine osmolyte responses to polyol pertu rbations, male Wistar rats were fed normal diet, the AR inhibitor sorb inil (at 40 mg/kg/d), 25% galactose, or a combination, for 10, 21 and 42 days. All animals at 21 days had higher apparent renal AR activity than at 10 or 42 days, possibly providing resistance to sorbinil. Sorb inil feeding alone tended to increase urinary, plasma and renal urea l evels. It reduced AR activity and sorbitol contents in renal inner med ulla, though less so at 21 days; other renal osmolytes, especially bet aine, were elevated. Galactose feeding caused little change in renal A R activity, and resulted in high galactose and galactitol contents in renal medulla, urine, blood and lens (and higher renal Na+ contents at 10 days). Renal sorbitol, inositol and GPC decreased, while betaine c ontents trended higher at all times. Sorbinil-galactose feeding reduce d renal AR activities and galactitol contents (again less so at 21 day s), urine, blood and lens galactitol, and further reduced renal sorbit ol contents. At 10 and 21 days it tended to raise renal betaine more, and restore inositol (but not GPC) contents to control levels. At 42 d ays it reduced renal and urinary Na+ and galactose, and decreased rena l betaine to control levels. Under most conditions, total renal (non-u rea) organic osmolyte contents (presumed to be mostly intracellular) a nd Na+ plus galactose contents (presumed mostly extracellular) changed together such that cell volumes may have been maintained. The excepti on was 10 days on galactose, where total osmolytes appeared too low. I n galactose-fed animals, urine/plasma ratios suggest some renal galact itol efflux, and cellular galactitol probably helps maintain osmotic b alance rather than cause swelling.