The role of organic osmolytes in the cerebral cell volume regulatory response to acute and chronic renal failure.

Abstract

Brain cells respond to increased osmolality of the extracellular fluid by accumulating inorganic electrolytes and nonperturbing organic osmolytes to limit the extent of brain cell shrinkage. It is unclear whether urea is an effective osmole that triggers this adaptive response. Therefore, the amount of brain water and the cerebral content of organic osmolytes in rats with acute renal failure induced by bilateral ureteral ligation and in animals with chronic renal failure for 6 weeks created by a 75% reduction in renal mass were measured. Eight hours after the onset of acute renal failure, the BUN concentration and serum osmolality were 61 +/- 4 mg/dL and 314 +/- 2 mosmol/kg, respectively, compared with 13 +/- 1 mg/dL and 288 +/- 1 mosmol/kg, respectively, in sham-operated rats. This hyperosmolal state reduced brain water from 79.7 +/- 0.1% in controls to 79.2 +/- 0.1% in uremic animals (P < 0.01). During acute renal failure lasting 48 h, the BUN concentration and serum osmolality rose to 251 +/- 10 mg/dL and 370 +/- 4 mosmol/kg versus 18 +/- 1 mg/dL and 286 +/- 4 mosmol/kg, respectively, in sham-operated control rats. The percentage of brain water content was unchanged in rats with azotemia for 48 h--79.6 +/- 0.1 compared with 79.5 +/- 0.2% in controls. Stabilization of brain volume was associated with a 19% increment in total organic osmolyte content in brain cells from 123 +/- 6 to 146 +/- 2 mmol/kg dry wt (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)