Effects of alterations in urine flow rate on prostaglandin E excretion in conscious dogs

Abstract

The relationships between urinary prostaglandin E excretion and urine flow rate were evaluated in 11 conscious mongrel dogs during antidiuresis, maximal water loading, vasopressin administration during maximal water loading, and mannitol infusion. Urine flow rates between 0.21 and 15.1 ml/min were achieved. Urinary prostaglandin E excretion rates, determined by a membrane receptor assay, varied directly with urine flow rates (r = 0.908). Vasopressin administration (34--540 microU . kg-1 . min-1) resulted in a fall, rather than the expected rise, in urinary prostaglandin E excretion. When the concentration of prostaglandin E in the urine was plotted against urine flow rate, the demonstrated relationship appeared most consistent with passive diffusion. Mannitol infusion increased urine flow rates to levels comparable to the levels seen with maximal water loading but did not result in a fall in plasma osmolality. Urinary prostaglandin E excretion rates, however, were not distinguishable from those in the previous group. These data demonstrate that urinary prostaglandin E excretion rates are determined, to a great extent, by urine flow rate and that the significance of the interpretation of elevated excretion levels of these lipids in diuretic states may have to be reevaluated.

Furosemide increases urine 6-keto-prostaglandin F1 alpha. Relation to natriuresis, vasodilation, and renin release.

“…Factors such as urinary volume 21 and sodium excretion 40 have been reported to affect PGEj excretion, but, in contrast, in our experiments these variables did not correlate with U6kV. However, while it is generally recognized that urine PGF^ is mostly of renal origin, no comparable data exist for 6-ketoPGF, 0 .…”

“…19 Second, while intrarenal infusion of PGEj does increase renal blood flow, administration of PGF^ in large doses does not prevent or completely reverse the decrease in renal blood flow in anesthetized animals caused by PG synthesis inhibitors. 20 Third, urine PGEj excretion, often taken as a measure of renal PGE 2 synthesis, may be affected by urine volume, 21 and therefore such excretion may be difficult to interpret when urine volume is increased by furosemide.…”

Effect of tienoxolol, a new diuretic β‐blocking agent, on urinary prostaglandin excretion in the rat

“…Prostaglandin excretion is maximal within 15 to 40 min returning to control excretion rates 1 to 2 h following either oral or intravenous doses of furosemide (Scherer & Weber, 1979;Wilson et al, 1982), this gives an unchanged net excretion rate when urine is collected for more than 2 h. These data confirm that factors such as urinary volume are able to affect prostaglandin excretion (Kirschenbaum & Serros, 1980) and, on the other hand, suggest that the time course of urinary prostaglandin excretion induced by tienoxolol could be different from that of furosemide. Furthermore, the latter is a much more potent diuretic agent than tienoxolol so that urinary volume probably does not play a role as important as with furosemide.…”

Reduction of urinary excretion of PGE2 and 6 keto PGF1α by tiaprofenic acid

“…Berl et al, 1977) and the maximal percentage inhibition elicited can be variable . Nevertheless, the results ofthe present study in saline-infused rats clearly demonstrate that tiaprofenic acid is an effective prostaglandin synthesis inhibitor and that it is approximately equipotent with indomethacin, although this comparison is complicated by different latencies of the inhibitory effect for the two drugs, and may also be affected by factors such as different changes in urine flow (Kirschenbaum & Serros, 1980) or pH with different inhibitors. However, there was no evidence that tiaprofenic acid inhibited PGI2 synthesis (as measured by 6 keto PGF1I excretion) less than PGE2 synthesis, at any of the doses employed or that tiaprofenic acid was different from indomethacin in the degree of inhibition of PGI2 synthesis elicited.…”