AJP - Renal Physiology, Vol 259, Issue 5 733-F738, Copyright © 1990 by American Physiological Society
Effects of an aldose reductase inhibitor on organic osmotic effectors in rat renal medulla
P. H. Yancey, R. G. Haner and T. H. Freudenberger
Biology Department, Whitman College, Walla Walla, Washington 99362.
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.
