The role of polyols in cerebral cell volume regulation in hypernatremic and hyponatremic states

Abstract

To clarify the role of the sugar polyols, sorbitol and myo-inositol, in cerebral cell volume regulation, we studied the effect of sorbinil, an inhibitor of aldose and aldehyde reductase, on the size of the cerebral water compartments in rats with hypernatremia, hyponatremia and normonatremia. Experimental animals were pretreated with sorbinil, while comparison rats received the drug vehicle. Rats were made hypernatremic for 96 h by water deprivation and injections of hypertonic saline, while hyponatremia was provoked over 48 h by daily administration of 5% dextrose in water and vasopressin. Sorbinil treatment was continued throughout the hyper- and hyponatremic periods. The severity of hypernatremia and hyponatremia was similar in sorbinil-treated and corresponding vehicle-treated rats. Brain electrolyte content and the size of the cerebral intracellular water compartment were comparable in sorbinil-treated rats vs. controls under hypernatremic and hyponatremic conditions. Sorbinil reduced the cerebral sorbitol content by approximately 50%, irrespective of the serum Na+ concentration. In contrast, sorbinil had no effect on brain myo-inositol content which rose by 114% during chronic hypernatremia (P less than 0.0001). Cerebral levels of myo-inositol did not decline in hyponatremic rats. We conclude that (1) sorbitol is not an essential cerebral osmolyte; and (2) myo-inositol is involved in the maintenance of brain cell volume during severe hypernatremia but not under hyponatremic conditions.