Aldosterone receptor blockade and the role of eplerenone: evolving perspectives

Recent observations clearly indicate that it is no longer appropriate to consider that the endocrine or paracrine properties of aldosterone are restricted to what has been called 'classic target cells'. These recently delineated haemodynamic and humoral actions of aldosterone have important clinical implications for the pathogenesis of both cardiovascular disease and progressive renal disease and consequently should influence future antihypertensive strategies. Although ACE inhibitors are very effective in retarding disease progression, there may be additional benefit achieved with concurrent aldosterone receptor blockade. As observed in clinical studies of congestive heart failure, including the recent EPHESUS study, as well as in animal models of renal disease, antagonism of aldosterone protects against progression of end-organ damage through both haemodynamic and direct cellular actions. With the recent advent of the SAB eplerenone, it is now feasible to conduct 'proof of principle' antihypertensive studies to assess whether end-organ damage, endothelial dysfunction and progressive renal disease can be more effectively prevented, without the dose-limiting side effects of non-selective aldosterone receptor blockade. Demonstration that selective aldosterone receptor blockade can retard progression of both cardiovascular and renal disease constitutes an important platform for advocating the addition of SABs to the therapeutic regimen used currently for attenuation of the cardiac, vascular and renal dysfunction of hypertension.