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 kidney. For this purpose, sorbitol content, aldose-reductase activity and sorbitol-dehydrogenase activity were determined in papilla from fetuses and 24-h-old neonates. After birth, no significant difference was observed in sorbitol content, whereas sorbitol-dehydrogenase activity decreased and aldose-reductase activity doubled. Changes in aldose-reductase activity were due to an increased number of enzymatic sites but not with a change in affinity. Low levels of sorbitol were found in fetal and neonatal medulla together with low levels of urine osmolarity. In neonates, sorbitol contents were tenfold lower than in the adult, probably as a result of a lower affinity and a lower number of enzymatic aldose-reductase sites. Attempts to increase the activity of polyol pathway in fetal kidney were made by means of hyperglycemic animals; this approach resulted in an increase of aldose-reductase activity without any change in sorbitol content. Our results indicate that, in fetal and neonatal kidneys, aldose-reductase activity is probably not the limiting factor for sorbitol synthesis: another parameter such as the availability of NADPH, might explain the low efficiency of the polyol pathway during the perinatal period.