Metabolic studies of uridine in rats with DOCA-salt hypertension and on high sodium diet.

1. The steady-state metabolic clearance and calculated secretion rate of the pyrimidine nucleoside uridine were studied by equilibrium infusion in normal rats, rats on a high sodium diet, rats made hypertensive by subcutaneous injection of deoxycorticosterone acetate (DOCA), unilateral nephrectomy and high sodium drinking fluid, and two control groups of rats for the hypertensive group. 2. Basal plasma uridine concentration in DOCA-salt hypertension rats was found to be significantly reduced to 3.99 +/- 0.31 mumol/L (mean +/- s.e.m.) compared with control rats (11.98 +/- 1.64 mumol/L). Metabolic clearance (MCR) in DOCA-salt hypertensive rats was significantly raised (200.54 +/- 10.77 mL/kg per min) compared with control rats (65.17 +/- 1.99 mL/kg per min). No difference was found in plasma uridine concentration and MCR among the other two control groups and high sodium diet rats. Calculated secretion rate was unchanged in all animals. No significant differences were found between different groups of rats in blood pressure responses to uridine. 3. The raised metabolic clearance and reduced plasma uridine concentration in DOCA-salt hypertension may be consistent with increased intracellular transport and phosphorylation of uridine to the physiologically active compound uridine monophosphate (UMP) which would lead to arteriolar constriction, hypertension and natriuresis. The results contrast with those in humans with extracellular fluid (ECF) expansion from endstage renal failure and rats with one-kidney, one-clip (1K1C) hypertension but are not due to the pharmacological effects of deoxycorticosterone. The difference may be due to the haemodynamic consequences of reduced renal perfusion pressure or reduced renal mass compared with DOCA-salt model.

Metabolism of uridine in expanded extracellular volume states.

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 mumol/L, 4.37-13.74 mumol/L median, interquartile range, and 2.64 mumol/L 2.51-2.74 mumol/L, respectively, P < 0.001). Plasma uridine was significantly diminished after isotonic fluid removal by ultrafiltration (UF) from 7.25 mumol/L (3.7-11.08) to 5.07 mumol/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 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)