It was once thought that aldosterone was a hormone released purely from the adrenal cortex, which circulated in the bloodstream and acted only on the kidneys to retain sodium and excrete potassium. This is now recognised to be a gross oversimplification (table 1).

NEW BIOLOGY OF ALDOSTERONE

The first novel finding discovered about aldosterone is that it is made locally in various different tissues in the body including the brain, vascular tissue, and the myocardium.^1,2 In heart failure, myocardial tissue synthesises even more aldosterone. The second novel finding is that mineralocorticoid receptors which are activated by aldosterone are in fact also widespread in the body including the brain, vascular tissue, and the myocardium. This means that aldosterone may act in a paracrine fashion in many tissues—that is, locally made aldosterone may act on local aldosterone receptors to mediate local (mostly adverse) effects. This may be one of many reasons why baseline plasma aldosterone values appear to only poorly predict the efficacy of aldosterone blockade. Other reasons may also explain this (see below and table 2).

However, the main revolution in our new understanding of aldosterone is that it has now been shown to mediate a host of different adverse biological effects in the body, which have only been recognised in the last 10 years. These effects range from vascular endothelial dysfunction to inflammation to widespread tissue injury and repair. These were often first seen in animal models and then found also in man.

In vitro studies showed first that aldosterone reduced nitric oxide produced in response in inflammatory stimuli. In experimental animals in vivo, aldosterone was then found to produce a vascular inflammatory response which is characterised not only by increased expression of …