ISCHEMIA-INDUCED CHANGES IN CELL ELEMENT COMPOSITION AND OSMOLYTE CONTENTS OF OUTER MEDULLA

The effect of 60 minutes of ischemia and subsequent reflow on cell ele ctrolyte and water homeostasis in the rat renal outer medulla was stud ied by determining sodium, potassium, chloride and phosphorus concentr ations and dry weights in individual tubule cells using electron micro probe analysis. HPLC was employed to measure glycerophosphorylcholine, betaine, inositol and sorbitol, as well as several free amino acids i n cortical and outer medullary tissue. Ischemia caused cell sodium and chloride concentrations to rise and cell potassium and phosphorus con centrations and cell dry weights to fall. These changes were most pron ounced in the proximal straight tubule (PST) cells, less in thick asce nding limb (MAL) and outer medullary collecting duct (OMCD) dark cells and barely noticeable in OMCD light cells. Except for some PST cells these changes were almost completely reversed 60 minutes after reintro ducing blood flow. After 24 hours of reperfusion the number of PST cel ls exhibiting deranged electrolyte homeostasis was greatly increased. The contents of glycerophosphorylcholine, betaine or inositol in the c ortex and outer medulla were not affected immediately following ischem ia. After 24 hours of reperfusion, the cortical contents of osmolytes were still normal, while outer medullary contents were reduced. Except for low glycine contents, the ischemia-induced changes in amino acid contents were reversed after 24 hours of reflow in the cortex, whereas in the outer medulla aspartate, glycine and taurine contents were dim inished. These results indicate increasing manifestation of PST cell i njury in the reflow period. The defective re-accumulation of organic o smolytes and free amino acids in the outer medulla during reflow may r eflect reduced interstitial tonicities, or may be due to inappropriate cellular uptake, synthesis or/and release. In view bf the known prote ctive properties of glycine, the postischemic depletion of cortical an d outer medullary glycine contents possibly contributes to the establi shment of postischemic acute renal failure.