RAPID CORRECTION OF HYPONATREMIA PRODUCES DIFFERENTIAL-EFFECTS ON BRAIN OSMOLYTE AND ELECTROLYTE REACCUMULATION IN RATS

Studies from these and other laboratories have shown that hyponatremia causes marked depletion of both electrolytes and organic osmolytes from the brain. The present studies evaluated brain reaccumulation of both classes of solute after correction of chronic hyponatremia. Hyponatremia was induced by subcutaneous infusions of 1-deamino-[8-D-arginine]-vasopressin (dDAVP) in rats fed a balanced liquid diet. After 14 days of sustained hyponatremia the dDAVP minipumps were removed causing rapid correction of plasma sodium concentrations from 104 +/- 1 mmol/l to 139 +/- 1 mmol/l in 24 h. Water and solute contents were measured in brain extracts both before and for 5 days after correction of the hyponatremia, and compared to values in normonatremic rats maintained on the same diet for 14 days. Our results demonstrate that electrolytes, particularly Na+ and Cl-, reaccumulate rapidly in the brain, resulting in a significant overshoot above normal control brain Na+ and Cl-contents as early as 24 h after correction. In contrast, organic osmolyte reaccumulation occurs more slowly, requiring 5 or more days for a return to normal control brain contents in most cases. A prominent exception to this pattern was glutamate, which also returned rapidly to normal brain contents within 24 h similar to the electrolytes. Quantitative analysis of brain water and solute contents after correction of hyponatremia indicated that the reaccumulation of electrolytes and organic osmolytes was sufficient to account for the changes in brain volume that occurred. Electrolytes accounted for 91-96% of the brain volume regulation during the first 24-48 h after correction of hyponatremia, but over longer periods of time organic osmolytes replaced some of the initial electrolyte gains and accounted for approximately one-third of the observed volume regulation by 5 days after correction of hyponatremia. These results therefore demonstrate markedly dissimilar patterns of reaccumulation of different classes of solutes in brain tissue following correction of chronic hyponatremia, which may be of significance for the pathological brain demyelination often seen under these conditions.