The effect of saluretics and spironolactone on aldosterone production and electrolyte excretion in man

Summary

Healthy volunteers received orally the saluretics furosemide (40 mg/day) and thiabutazide (10 mg/day) over a 5-day period, and the aldosterone antagonist spironolactone (5 mg and 10 mg/kg per day) over 7-and 3-day periods, respectively. On the first day of treatment both saluretics induced a marked increase in sodium and water excretion, but only a moderate increase in potassium excretion. On the second day, however, the sodium and water excretion had already returned to almost normal values, reaching a minimum after discontinuation of the saluretics. Under saluretic therapy, a steep increase in plasma aldosterone concentration and in urinary aldosterone was observed. After the saluretics were discontinued, both the markedly elevated plasma aldosterone concentration and the aldosterone excretion returned to normal within two days. Under saluretic therapy potassium excretion appeared to be aldosterone-dependent, since potassium excretion paralleled aldosterone excretion. Spironolactone (5 mg/kg oder a 7-day period) caused a moderate increase in sodium excretion and a moderate decrease in potassium excretion. Spironolactone (10 mg/kg over a 3-day period) caused a distinct increase in sodium excretion and a slight decrease in potassium excretion. Neither of the two spironolactone doses used here produced an increase in aldosterone excretion. After discontinuation of spironolactone, a rebound in aldosterone excretion was observed. The increase in aldosterone excretion was associated with corresponding changes in electrolyte excretion.

The increase in aldosterone excretion and in plasma aldosterone concentration induced by the saluretic thiabutazide was markedly reduced by the administration of spironolactone (10 mg/kg). The sodium and water retention which was caused by the hyperaldosteronism, was almost completely abolished, and the increased potassium excretion returned to normal.