Is urinary flow rate a major regulator of prostaglandin E excretion in man?

Urinary PGE2 excretion is enhanced in several polyuric states in man suggesting that PGE2 synthesis could be a mediator of diuresis. To explore the alternate hypothesis that polyuria is the cause of the increased PGE2 excretion, we increased urine flow rate by intravenous administration of dextrose and water with different magnesium, calcium and potassium solutions in four normal males. Urinary PGE excretion rose in parallel with urine volume (r = 0.65 p < 0.01) independently of the electrolyte solution. To determine the effects of chronic alterations in water balance in 5 female subjects, we sequentially regulated oral water intake to induce 1, 2, 4 and 8 liters of urine volume/day. During low (40 mEq) sodium diets, PGE increased from 540 +/- 50 to 4880 +/- 1240 ng/d with increasing urinary volume (r = 0.81, p < 0.01). Similarly, for 200 mEq sodium intake PGE paralleled urinary volume (from 630 +/- 100 to 4740 +/- 800 ng/d, r = 0.61, p < 0.01). In vitro sample dilution studies demonstrated no interference from method blank, and the addition of thin layer chromatography prior to Sephadex chromatography failed to alter assay measurements. We conclude that extreme increases in urinary flow rate may directly enhance PGE excretion in man.