1. The effects of frusemide, hydrochlorothiazide and spironolactone on the renal prostaglandin system, and the interference with their diuretic and natriuretic effects by inhibition of prostaglandin synthase, were investigated in healthy human subjects.
2. Urinary excretion of prostaglandin E2 was increased by the administration of frusemide (P < 0.05), hydrochlorothiazide and particularly by spironolactone, the least potent natriuretic agent (P < 0.05). A qualitatively similar but statistically insignificant rise in excretion of prostaglandin F2α was observed with hydrochlorothiazide.
3. The rise in urinary excretion of sodium after frusemide and hydrochlorothiazide was significantly reduced by indomethacin, which also abolished the potassium-sparing effect of spironolactone and partially suppressed the diuretic-induced rise in plasma renin activity.
4. Indomethacin had no significant effect on urinary osmolality or free water absorption in the presence of frusemide or hydrochlorothiazide, but markedly enhanced urinary osmolality (P < 0.05) and free water absorption (P < 0.05) in the presence of spironolactone.
5. Increased renal prostaglandin activity after frusemide, hydrochlorothiazide and spironolactone may contribute to their natriuretic action which, in addition to the antikaliuretic effect of spironolactone, may be partially abolished by the presence of non-steroidal antiphlogistic agents.