Skeletal muscle contains high levels of aldose reductase that catalyze
s the reduction of galactose to the polyol galactitol. Galactitol and
water were measured in muscle of rats fed a high galactose diet with o
r without addition of the aldose reductase inhibitor sorbinil. Galacti
tol, measured in isolated samples of muscle by HPLC, reached steady-st
ate levers (5.9 +/- 1.0 mg/g tissue) within 3 days. Muscle water, dete
rmined in vivo by magnetic resonance imaging, increased (51 +/- 5%, P
< 0.02) to steady-state levels within 7 days. Both the increased galac
titol and water remained constant for the 4-month duration of this stu
dy. Aldose reductase activity also remained constant. Sorbinil prevent
ed both the increase in galactitol and the increase in water. These re
sults suggest that the increase in water is due to the osmotic effects
of galactitol accumulation and demonstrate that galactitol and water
accumulation neither up-regulate nor down-regulate aldose reductase ex
pression in skeletal muscle,