Effect of sustained water diuresis on prostaglandin E2 excretion in humans

The relationship of the renal excretion of prostaglandin E2 (PGE2) to urine flow during a water diuresis was examined using radioimmunoassay (RIA) and gas chromatography-mass spectrometry (GC-MS). Seven normal women fasted overnight were water loaded with 20 ml/kg orally, and each hour for 3 h they drank water to replace the urine volume plus 20 ml. The osmolality of the collected urines ranged from 49 to 1,073 mosmol/kg. Assay of urinary PGE2 concentrations by both RIA and GC-MS gave a correlation coefficient of 0.94. Eight normal women were then studied with a water diuresis sustained for 6 h. The excretion of PGE2 (measured with the validated RIA) increased for the 1st 2-3 h (from 1.8 +/- 0.5 to 25.8 +/- 16.6 pg X kg-1 X min-1), but then fell to base-line level by the 5th h (to 2.9 +/- 0.8 pg X kg-1 X min-1) even though the water diuresis was sustained. The urinary concentration vs. time curves for PGE2 and for the freely diffusible solute urea were compared. PGE2 concentration remained elevated for 3 h before falling (from the 100 pg/ml range to 15 pg/ml) while urea concentration decreased steadily from the 1st h. This finding suggests that the early urinary PGE2 excretion was not a washout phenomenon and is consistent with a transient increase in PGE2 synthesis. We conclude that urinary excretion of PGE2 is not a simple function of urine flow after a water load. There is a transient initial increase in urinary PGE2 excretion at the start of a water load that probably reflects an increase in renal PGE2 synthesis. However, with a sustained water diuresis, PGE2 excretion falls, indicating that an enhanced PGE2 synthesis rate is not required to sustain a water diuresis.