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

Abstract

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.