High urine flow rate increase prostaglandin E excretion in the conscious dog

Although previous studies from this and other laboratories have shown that urinary prostaglandin E excretion (UPGEV) can very independent of urine flow rate, recent studies during water diuresis in the conscious dog have suggested that high urine flow rate per se may increase UPGEV. To examine the effect of urine flow rate on UPGEV we administered either mannitol, chlorothiazide or Ringer's solution to mongrel dogs and measured UPGEV. During anesthesia neither mannitol or chlorothiazide increased UPGEV. There was, however, a consistent increase with all three agents in awake animals. This increase in UPGEV was independent of alterations in glomerular filtration rate. There was a consistent increase in urinary sodium excretion and decrease in urinary osmolality with all three agents. The changes in PGE, however, were similar to those found during water diuresis when no increase in sodium excretion was found. It is not presently clear whether these findings reflect a true increase in renal PGE synthesis due to some changes in flow or pressure within the renal medulla or rather represent unchanged PGE synthesis by renal tubular cells, the high tubule fluid flow rate causing increased entry into the tubular lumen in contrast to the renal interstitium.