Survival in Hostile Environments: Strategies of Renal Medullary Cells

摘要

Cells in the renal medulla exist in a hostile milieu characterized by wide variations in extracellular solute concentrations, low oxygen tensions, and abundant reactive oxygen species. This article reviews the strategies adopted by these cells to allow them to survive and fulfill their functions under these extreme conditions. The renal medulla is the only place in the mammalian organism where cells are exposed routinely to widely varying extracellular osmolalities (79, 128). In antidi-uresis, interstitial osmolalities may be several-fold higher in the papilla than in systemic plasma, whereas in diuresis values close to isoosmolality are found (13). NaCl and urea concentrations of an order of magnitude such as those occurring in the inner medulla inantidiuresis severely compromise the viability of most animal cells. In addition, efficient urinary concentration is inevitably associated with low oxygen tensions within the renal medulla. Medullary hypoxia results from 1) the relatively low blood flowthrough the medulla, a necessary prerequisite for the maintenance of the high interstitial papillary tonicity, 2) oxygen diffusion from descending to ascending vasa recta (AVR), and 3) the high metabolic demands of medullary cells [particularly the medullary thick ascending limbs (mTAL)] (18, 79, 91). Finally, in addition to osmotic stress and low oxygen tension, medullary cells are exposed to elevated concentrations of reactive oxygen species (ROS) produced by mTAL and vasa recta cells (FIGURE 1) (75,134).