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Prostaglandins and renal NaCl excretion in healthy human subjects: Effects of prostaglandin synthesis inhibition with indomethacin

Die Rolle von Prostaglandinen bei der Regulation der renalen NaCl Ausscheidung: Untersuchungen an gesunden Versuchspersonen während Hemmung der Prostaglandinsynthese mit Indometacin


The effect of a single oral dose of 75 mg of indomethacin on renal function and urinary excretion of prostaglandin (PG) E2 was investigated in six healthy volunteers. In the absence of changes in GFR, indomethacin significantly reduced urinary excretion of sodium and chloride for 12 h with a return to control values afterwards. This effect on the renal excretory function was closely paralleled by a decrease in urinary excretion of PGE|12|0 which also returned to control values after 12 h. In a second series of experiments, inhibition of PG synthesis was performed in healthy volunteers during sustained water diuresis to determine the tubular site of altered NaCl absorption using clearance methods. Again, indomethacin induced a significant suppression of urinary excretion of sodium, chloride and potassium without changes in GFR or urinary excretion of phosphate. Indomethacin treatment had no effect on the delivery of chloride beyond the proximal tubule to the distal tubules (distal delivery) but significantly increased the distal fractional absorption of chloride (DFACl). In a third series of experiments, the effect of furosemide on GFR and tubular NaCl absorption was studied without and with concomitant administration of indomethacin. Furosemide induced an almost twelvefold increase in the urinary excretion of sodium and chloride, an approximately threefold increase in urinary excretion of potassium and a significant increase in urinary phosphate excretion. Furosemide also increased distal delivery and decreased DFACl and also increased urinary excretion of PGE2. Concomitant indomethacin treatment significantly suppressed urinary excretion of PGE2 but did not affect any of the furosemide induced changes in renal function. Our results support the concept that PG participate in the regulation of renal NaCl excretion and suggest that the diluting segments of the nephron may be the site of action of renal PG. Furthermore, furosemide stimulates renal synthesis of PGE2 but the tubular effects of this diuretic appear not to be mediated by the renal PG system.


An sechs gesunden Versuchspersonen wurde die Wirkung einer oral verabreichten Einzeldosis von 75 mg Indometacin auf die Nierenfunktion und die Urinausscheidung von Prostaglandin (PG) E2 untersucht. Indometacin bewirkte eine signifikante Reduktion der NaCl Ausscheidung über einen Zeitraum von 12 h ohne gleichzeitige Wirkung auf die GFR. Diese Wirkung auf die exkretorische Nierenfunktion war von einer gleichzeitigen Abnahme der Urinausscheidung von PGE2 begleitet, welche ebenfalls nach 12 h wieder auf Kontrollwerte anstieg. In einer zweiten Versuchsserie wurde die Wirkung einer Indometacingabe auf proximale und distale Tubulusfunktion während Wasserdiurese mittels Clearance-Methoden ermittelt. Dabei kam es nach Indometacingabe wiederum zu einer signifikanten Reduktion der Urinausscheidung von Chlorid, Natrium und Kalium ohne Änderungen der GFR oder der Urinausscheidung von Phosphat. Die Indometacingabe hatte keinen Effekt auf die Chloridmenge, die den distalen Tubulus erreicht (distal delivery), führte jedoch zu einem signifikanten Anstieg der distalen fraktionellen Absorption von Chlorid (DFACl). In einer dritten Versuchsserie wurde die Wirkung von Furosemid auf die GFR und die tubuläre NaCl Absorption ohne und mit gleichzeitiger Gabe von Indometacin untersucht. Nach Gabe von Furosemid kam es zu einem fast zwölffachen Anstieg der Urinausscheidung von Natrium und Chlorid, einem etwa dreifachen Anstieg der Urinausscheidung von Kalium und einem signifikanten Anstieg der Urinausscheidung von Phosphat. Weiterhin kam es nach Furosemidgabe zu einem signifikanten Anstieg der “distal delivery”, einer Abnahme der DFACl und einem Anstieg der Urinausscheidung von PGE2. Unter gleichzeitiger Gabe von Indometacin kam es zu einer signifikanten Abnahme der Urinausscheidung von PGE2 ohne daß die Furosemid-induzierten Änderungen der exkretorischen Nierenfunktion dadurch verändert wurden. Unsere Ergebnisse legen eine Rolle des endogenen PG-Systems bei der Regulation der renalen NaCl Ausscheidung nahe und lokalisieren eine solche Wirkung in das Verdünnungssegment des distalen Tubulus. Furosemide vermag die renale Synthese von PGE2 zu stimulieren aber die tubuläre Wirkung dieses Diuretikums scheint nicht über das renale PG System vermittelt zu werden.

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Author information

Correspondence to Dr. R. Düsing.

Additional information

Dedicated to Professor F. Krück on the occasion of his 60th birthday

This study was supported by research grant No. FA-8476, Ministerium für Wissenschaft und Forschung NRW, FRG

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Düsing, R., Kipnowski, J. & Kramer, H.J. Prostaglandins and renal NaCl excretion in healthy human subjects: Effects of prostaglandin synthesis inhibition with indomethacin. Klin Wochenschr 60, 1229–1233 (1982).

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Key words

  • Prostaglandins
  • NaCl excretion
  • Excretory renal function
  • Tubular function


  • Prostaglandine
  • NaCl Ausscheidung
  • Exkretorische Nierenfunktion
  • Tubuläre Funktion