Aldose reductase and myo-inositol transporter mRNA are independently regulated in rat renal medulla.

Abstract

During antidiuresis, renal papillary cells accumulate organic osmolytes preferentially over inorganic ions. It has been previously demonstrated that sodium infusion increased all of these organic osmolytes except myo-inositol (1). Conversely, urea infusion increased only glycerophosphorylcholine significantly. In addition to sodium and urea, potassium localized in tissue and urine influenced the composition of organic osmolytes. The goal of this study was to clarify how the level of mRNA of osmoregulatory protein is regulated by the extracellular solutes and how it affects the accumulation of organic osmolytes. To clarify the relationship between intra- or extracellular solutes and the regulation of Na/myo-inositol cotransporter and aldose reductase, mRNA of these osmo-regulatory proteins were determined in water-deprived sodium chloride-, potassium chloride-, and urea-loaded rats. Medullary content of sorbitol and myo-inositol, and aldose-reductase enzymatic activity were measured simultaneously in these animals. In water-deprived, sodium-loaded, and potassium-loaded rats, the inner medullary sorbitol content increased significantly in accordance with the rise in the enzymatic activity and the level of aldose reductase mRNA. In urea-loaded rats, both the sorbitol content and the level of aldose reductase mRNA were equal to that in hydrated rats. In the outer and inner medullary tissues, the level of myo-inositol transporter mRNA was increased in all hyperosmolality protocols, including urea infusion, which corresponded with the rise in myo-inositol content. In conclusion, potassium chloride infusion is as effective as water deprivation and sodium chloride infusion in raising the level of aldose reductase and myo-inositol transporter mRNA, whereas urea influenced only myo-inositol transporter. Although aldose reductase and myo-inositol transporter are osmoregulatory proteins in the renal medulla, the levels of aldose reductase and sodium-dependent myo-inositol transporter mRNA are regulated independently.