A dual effect of nonsteroidal anti-inflammatory drugs on renal water handling in humans.
The role of renal prostaglandins (PGs) in the induction and maintenance of a sustained water diuresis was studied by using two different nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and meclofenamate given either before or during the diuresis. Urinary PGE2 excretion increased with the initiation of a water diuresis (from 2.5 +/- 0.7 to 6.1 +/- 1 pg/kg/min during the 2nd hr, P less than .01) but then fell back to control levels when water diuresis was established. Pretreatment with NSAIDs abolished the initial increase in PGE excretion and delayed the onset of the water diuresis so that 1 hr after the initiation of the diuresis, the urine osmolality in the control subjects was 205 +/- 50 mosm/kg as compared with 440 +/- 55 mosm/kg (P less than .05) for the NSAID-treated subjects. In contrast, the urine osmolality did not change when subjects were given the NSAIDs 5 hr after the onset of the water diuresis. However, the NSAIDs did decrease urine volume and free water clearance for as long as the urinary PG excretion was suppressed, regardless of when the drugs were given. This action of the NSAIDs to decrease the urine volume and free water clearance was due to a decrease in delivery of water and solute to the diluting segments of the nephron. These data imply that the transient increase in urinary PGE excretion occurring at the onset of a water diuresis has functional significance, as NSAIDs block the increase in PG synthesis and also interfere with the onset of a water diuresis by delaying the attainment of a maximally dilute urine.(ABSTRACT TRUNCATED AT 250 WORDS)
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000652:urine; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D010710:Phosphates; D011453:Prostaglandins; D011458:Prostaglandins E; D008469:Meclofenamic Acid; D007213:Indomethacin