OSMOTIC ADAPTATION OF RENAL MEDULLARY CELLS DURING TRANSITION FROM CHRONIC DIURESIS TO ANTIDIURESIS

The cells of the renal medulla adapt osmotically to high extracellular tonicities by high concentrations of organic osmolytes. Intracellular accumulation of these. substances is, however, relatively slow. The a im of the present study was to assess the effect of an abrupt rise in extracellular tonicity on intracellular osmotically active substances after prior reduction of medullary contents of organic osmolytes by ch ronic diuresis. Intra- and extracellular electrolyte concentrations at the papillary tip and the tissue contents of methylamines (glyceropho sphorylcholine, betaine), polyols (myo-inositol, sorbitol), and severa l amino acids were determined in the different kidney zones by electro n microprobe analysis and high-performance liquid chromatography in co ntrol animals, in rats infused for 6 days with furosemide via osmotic minipumps, and in rats given the vasopressin analogue [deamino-Cys1, D -Arg8]vasopressin (DDAVP) after the chronic furosemide treatment. Chro nic diuresis greatly reduced interstitial tonicity and inner medullary contents of methylamines and polyols and moderately reduced inner med ullary amino acid contents but did not significantly affect intracellu lar electrolyte concentrations. When the diuretic rats were infused wi th DDAVP for 2 h, interstitial tonicity more than doubled and intracel lular K and Cl concentrations rose by approximately 60 and 160%, while inner medullary contents of methylamines, polyols, and amino acids we re not changed significantly. These data demonstrate that after effect ive depletion of medullary organic osmolytes by long-term diuresis, th e cells of the renal papilla adapt osmotically to an abrupt increase i n extracellular tonicities by elevated cell electrolyte concentrations . This rise in intracellular ionic strength depends not only on the ex tent of the change in extracellular tonicity but also on the amount of organ in osmolytes present in these cells before the hypertonic stres s.