Potassium depletion modulates aldose reductase mRNA in rat renal inner medulla

The organic osmolytes present in renal inner medullary cells balance the extracellular hyperosmolality and protect the cell against the effects of high salts and urea. We previously demonstrated that a renal concentrating defect due to potassium depletion was associated with a decrease in organic osmolytes including sorbitol. However, we could not determine whether a reduction in medullary organic osmolyte would be cause or effect of urine concentration defect associated with potassium depletion. We focused on the synthesis of sorbitol catalyzed by the enzyme, aldose reductase. To clarify whether the treatment of potassium depletion would affect aldose reductase when extracellular tonicity, and medullary sodium or potassium was maintained at the level of control rats, we administered a hypertonic solution of NaCl or KCl to potassium-depleted rats and evaluated aldose reductase enzymatic activity and mRNA abundance as well as the medullary contents of organic osmolytes. Either infusion significantly reduced tissue sodium content in potassium-depleted rats. With KCl infusion protocol but not that of NaCl, sorbitol as well as aldose reductase mRNA abundance increased to the control level. Medullary contents of other organic osmolytes exhibited a pattern similar to sorbitol. Data suggested that aldose reductase mRNA abundance was reduced in potassium depletion irrespective of medullary sodium content. A decrease in sorbitol level may precede a urinary concentrating defect. Our finding constitutes the first demonstration of the relationship between a potassium deficiency and the abundance of aldose reductase mRNA, an osmoregulatory protein in the kidney.