Cell survival in the hostile environment of the renal medulla.

The countercurrent system in the medulla of the mammalian kidney provides the basis for the production of urine of widely varying osmolalities, but necessarily entails extreme conditions for medullary cells, i.e., high concentrations of solutes (mainly NaCl and urea) in antidiuresis, massive changes in extracellular solute concentrations during the transitions from antidiuresis to diuresis and vice versa, and low oxygen tension. The strategies used by medullary cells to survive in this hostile milieu include accumulation of organic osmolytes and heat shock proteins, the extensive use of the glycolysis for energy production, and a well-orchestrated network of signaling pathways coordinating medullary circulation and tubular work.