Mechanism of the antimineralocorticoid effects of spironolactones

Abstract

Spirolactones are antimineralocorticoid compounds, which were intoduced into therapeutics in 1960. They are useful in the treatment of hyperaldosteronism and essential hypertension, although their side effects (gynecomastia, impotence, menstrual cycle abnormalities) limit their use. They are known to antagonize the effect of aldosterone at the level of the target cells, and until recently this mechanism was the only one generally implicated. In 1972, Erbler showed that spironolactone inhibits aldosterone biosynthesis in vitro. Since then, several authors have confirmed this effect, both in animals and man, and have therefore challenged the relative importance of peripheral aldosterone antagonism in favor of an inhibitory effect of these drugs on aldosterone biosynthesis. This editorial review attempts to clarify the findings and to determine whether antialdosterones act mainly at the target cell, or through inhibition of aldosterone production, or alternatively by a combination of each effect.