Effects of indomethacin on furosemide-stimulated urinary PGE₂ excretion in man

We studied the effects of furosemide on urinary excretion of PGE₂ and sodium and the effects of inhibition of prostaglandin (PG) synthesis with indomethacin or furosemide-induced PGE₂ excretion and natriuresis in normal man. Furosemide (20 mg i.v.) increased the urinary excretion of PGE₂ from 71.2 ± 17.2 to 255.9 ± 41.0 ng/4 h. Sodium excretion increased in parallel. Indomethacin, in a dose sufficient to decrease basal urinary PGE₂ excretion by 〉90%, significantly decreased both urinary PGE₂ and sodium excretion under furosemide without affecting delivery of furosemide into the urine. The urinary excretion of furosemide was 9.4 ± 0.4 and 9.3 ± 1.4 mg/24 h with and without indomethacin, respectively. However, the furosemide-induced encrement in PGE₂ excretion and sodium excretion over baseline was not changed. Furosemide-stimulated urinaary PGE₂ excretion correlated significantly with sodium excretion rate with and without indomethacin. Indomethacin changed the relationship between absolute amounts of furosemide in urine and PGE₂ excretion but did not affect the increment in excretion over baseline or the significant correlation of urinary PGE₂ with sodium excretion.