Effects of an aldose reductase inhibitor on organic osmotic effectors in rat renal medulla.

Renal medullary cells use sorbitol, betaine, and other organic compounds as osmotic effectors (osmolytes) to balance high extracellular NaCl. Excess sorbitol is also implicated in diabetes complications in several organs including kidneys. To study regulation of renal sorbitol, male Wistar rats were given an aldose reductase inhibitor, sorbinil, at 40 mg.kg-1.day-1 in food to block sorbitol formation from glucose. Inner medullas of kidneys were analyzed for osmolytes by high-performance liquid chromatography and atomic absorption. Animals on sorbinil had significantly reduced medullary sorbitol contents in a group on ad libitum water for 10 days (2.7 mmol/kg wet wt compared with 4.8 in controls) and in an antidiuretic group kept 7 days and an additional 3 days without water (3.8 mmol/kg wet wt compared with 7.2 in antidiuretic controls). In both groups, betaine contents were significantly elevated (9.2 mmol/kg wet wt compared with 5.5 in ad libitum water controls: 6.4 mmol/kg wet wt compared with 4.2 in antidiuretic controls). No other osmolytes differed. Total contents of nonurea organic osmolytes maintained a constant ratio to sodium contents; thus increased betaine concomitant with decreased sorbitol may have maintained constant cell volume. In contrast, in animals kept 21 days on sorbinil, there were significant decreases in urea and inositol contents. However, there were no significant differences in sorbitol or betaine compared with controls, suggesting a compensating increase in sorbitol production or in sorbinil removal.