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METABOLISM OF URIDINE IN EXPANDED EXTRACELLULAR VOLUME STATES
Author(s) -
Hasnain Quloobul,
Macdonald Graham,
Haupert Garner T.
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb01692.x
Subject(s) - extracellular , uridine , metabolism , extracellular fluid , chemistry , volume (thermodynamics) , biochemistry , medicine , rna , physics , thermodynamics , gene
SUMMARY 1. Uridine and uridine monophosphate (UMP) are natriuretic and a vasopressor in intact rats. In deoxycorticosterone acetate (DOCA)‐salt hypertensive rats metabolic clearance rate (MCR) of uridine is raised and basal plasma uridine diminished, suggesting that metabolism of uridine is linked to changes in extracellular space. 2. Plasma uridine concentration was raised in 38 patients with chronic renal failure compared with age‐ and sex‐matched healthy controls (8.49 μmol/L, 4.37–13.74 μmol/L median, interquartile range, and 2.64 μmol/L 2.51–2.74 μmol/L, respectively, P < 0.001). Plasma uridine was significantly diminished after isotonic fluid removal by ultrafiltration (UF) from 7.25 μmol/L (3.7–11.08) to 5.07 μmol/L (3.3–8.3), P < 0.001, whereas concentration of marker solutes urea and creatinine remained unchanged. During haemodialysis (HD), plasma uridine fell significantly from its pre‐HD level. 3. In an animal model of expanded extracellular space the one‐kidney, one‐clip rat, plasma uridine was significantly higher (20.56±1.19 μmol/L, P < 0.01) and MCR diminished (34.93 ± 3.44 mL/kg per min, P < 0.01) compared with sham‐operated animals (plasma uridine 12.14 ± 1.07 and MCR 53.59 ± 4.11 mL/ kg per min). Uridine or UMP did not inhibit Na + , K + ‐ATPase in either of the two assay systems. 4. It was concluded that catabolism of uridine is reduced by extracellular expansion and probably increased by volume reduction by UF. Such a function may be due to the presence of a hypertensive natriuretic factor postulated by Dahl and de Wardener (1980), but would not be consistent with the ouabain‐like factor postulated by other workers in this situation because it has no inhibitory effect on Na + , K + ‐ATPase.