Hyponatremia causes large sustained reductions in brain content of multiple organic osmolytes in rats

Abstract

Brain adaptation to hypoosmolality is known to involve volume regulatory losses of both extracellular and intracellular electrolytes. We studied the effects of acute and chronic hypoosmolality on brain content of organic osmolytes as well as electrolytes in rats to ascertain the relative contributions of different brain solutes to the brain volume regulation that occurs under these conditions. Brains were disserted from rats after 2, 7 and 14 d of sustained hyponatremia induced by continuous infusion of 1-deamino-[8-d-arginine]-vasopressin (DDVAP) in combination with a liquid formula, along with control rats fed the same formula in the absence of DDAVP infusions. One half of each brain was analyzed for organic osmolyte contents and the other half for water and electrolyte contents. Brain Na⁺, K⁺ and Cl⁻ and multiple organic osmolytes (glutamate, creatine, taurine, myo-inositol, glutamine and glycerophosphoryl-choline) decreased markedly by 2 d of hyponatremia, and brain electrolyte and most organic osmolyte contents then remained at these reduced levels throughout the duration of the hyponatremia. Although the absolute magnitude of the brain electrolyte losses was greater than the magnitude of the brain organic osmolyte losses, the organic osmolyte losses accounted for approximately 35% of the total measured brain solute losses during sustained hyponatremia. These results demonstrate that organic osmolytes constitute a significant proportion of the brain solute losses that take place during hyponatremia, and indicate that reductations in both organic osmolyte and electrolyte contents are necessary to accomplish brain volume regulation during adaptation to sustained hypoosmolality.