Factors affecting Potassium Balance During Frusemide Administration

1. We investigated the effects of Na⁺ intake, the renin-angiotensin-aldosterone system and antidiuretic hormone (ADH) on K⁺ balance during 3 days of frusemide administration to six normal subjects. Subjects received 40 mg of frusemide for 3 days during three different protocols: Na⁺ intake 270 mmol/day (high salt); Na⁺ intake 20 mmol/day to stimulate the renin-angiotensin-aldosterone system (low salt); Na⁺ intake 270 mmol/day plus captopril (25 mg/6 h) to prevent activation of the renin-angiotensin-aldosterone system. In a fourth protocol, a water load was given during high salt intake to prevent ADH release and then frusemide was given.

2. During high salt intake, frusemide increased K⁺ excretion (U_KV) over 3 h, but the loss was counterbalanced by subsequent renal K⁺ retention so that daily K⁺ balance was neutral.

3. During low salt intake, the magnitude of the acute kaliuresis following the first dose of frusemide and the slope of the linear relationship between U_KV and the log of frusemide excretion were increased compared with that found during the high salt intake. In addition, low salt intake abolished the compensatory renal retention of K⁺ after frusemide and cumulative K⁺ balance over 3 days of diuretic administration was uniformly negative (−86 ± 7 mmol/3 days; P < 0.001).

4. Captopril abolished the rise in plasma aldosterone concentration induced by frusemide. The acute kaliuresis after frusemide was unchanged compared with that observed during high salt intake. The compensatory reduction in U_KV occurring after the diuretic was slightly potentiated. In fact, captopril given without the diuretic induced a small positive K⁺ balance.

5. When a water load was given concurrently with frusemide, the acute kaliuresis was >30% lower compared with that seen with frusemide alone, even though the natriuretic response was unchanged.

6. We conclude that: (a) K⁺ balance is maintained when frusemide is given during liberal Na⁺ intake because acute K⁺ losses are offset by subsequent renal K⁺ retention; (b) this compensatory K⁺ retention can be inhibited by aldosterone release which could account for the negative K⁺ balance seen during salt restriction; (c) the short-term kaliuretic response to frusemide is augmented by release of both ADH and aldosterone whereas changes in K⁺ balance over 3 days of frusemide are dependent on plasma aldosterone concentration.