EFFECT OF HYPERGLYCEMIA ON THE POLYOL PATHWAY IN RAT-KIDNEY DURING THE PERINATAL-PERIOD

The activity of the polyol pathway was studied in developing rat kidne y. For this purpose, sorbitol content, aldose-reductase activity and s orbitol-dehydrogenase activity were determined in papilla from fetuses and 24-h-old neonates. After birth, no significant difference was obs erved in sorbitol content, whereas sorbitol-dehydrogenase activity dec reased and aldose-reductase activity doubled. Changes in aldose-reduct ase activity were due to an increased number of enzymatic sites but no t with a change in affinity. Low levels of sorbitol were found in feta l and neonatal medulla together with low levels of urine osmolarity. I n neonates, sorbitol contents were tenfold lower than in the adult, pr obably as a result of a lower affinity and a lower number of enzymatic aldose-reductase sites. Attempts to increase the activity of polyol p athway in fetal kidney were made by means of hyperglycemic animals; th is approach resulted in an increase of aldose-reductase activity witho ut any change in sorbitol content. Our results indicate that, in fetal and neonatal kidneys, aldose-reductase activity is probably not the l imiting factor for sorbitol synthesis: another parameter such as the a vailability of NADPH, might explain the low efficiency of the polyol p athway during the perinatal period.