Potassium homeostasis with indomethacin therapy in normal subjects

In an attempt to delineate effects of prostaglandin (PG) synthesis inhibition on potassium metabolism in normal subjects, we challenged 13 young, healthy volunteers with a potassium chloride infusion before and after a 4-day course of indomethacin (25 mg orally, three times a day). The plasma potassium level was monitored at 10-minute intervals throughout the 50-minute infusion and for a total of 180 minutes. The maximal increment in plasma potassium level was 0.82 +/- 0.07 mmol/L (mEq/L) in the untreated state, and 0.86 +/- 0.08 mmol/L with indomethacin treatment. The basal potassium level before infusion was higher in the indomethacin-treated than the control state (3.83 +/- 0.07 v 3.68 +/- 0.07 mmol/L; P less than 0.01). Urinary potassium excretion over the 3-hour study period equalled the potassium load administered, and was unaffected by indomethacin therapy. Indomethacin did not alter insulin or aldosterone levels during the study. PGE2 excretion over the 3 hours was lower in the indomethacin than the control phase, although it was higher than normal in both phases. In an additional experiment, the comparative effects of a saline versus saline-potassium infusion on PG excretion were studied. No differences were seen between the excretion patterns of PGE2 or 6-keto-PGF1a with the two infusions. We conclude that (1) although basal serum potassium level is slightly higher in healthy young people during indomethacin treatment, there is little effect on handling of an acute potassium load; (2) the aldosterone response to hyperkalemia is PG-independent; (3) urinary PG excretion increases in response to a saline-based infusion, but the effect is not enhanced by acute potassium loading.