Changes in tubular reabsorption of uric acid in response to alterations in the extracellular fluid volume (ECFV) were examined in rats by clearance studies and by direct intratubular microinjections. Contraction of the ECFV led to a rise in the serum uric acid concentration and a 47% decrease in the clearance of uric acid. The ratio of uric acid to inulin clearance also fell, indicating an increase in the net tubular reabsorption of urate. Volume expansion resulted in an increase in the urate clearance and a 37% decrease in the net tubular reabsorption of uric acid. To localize the site in the nephron where these changes occur, microinjections of [2 14C]urate were performed. The lack of conversion of radioactive urate to allantoin after microinjections was demonstrated by thin layer chromatography. After contraction of the ECFV, urinary recoveries of uric acid were significantly decreased after microinjections into proximal tubular sites. In contrast, recoveries were increased from these proximal sites after volume expansion. No evidence for distal reabsorption was obtained in any group of animals. These studies demonstrate that net urate reabsorption is influenced by the state of hydration of the ECFV and that these alterations are mediated by changes in the rates of reabsorption in the proximal tubule.
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