New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System: Mineralocorticoid-Receptor Blockers Exert Antihypertensive and Renoprotective Effects Independently of the Renin–Angiotensin System

The role of angiotensin II in mediating hypertension and renal diseases is well documented, and inhibition of the renin-angiotensin-aldosterone system elicits antihypertensive and renoprotective effects. There is increasing evidence implicating aldosterone, in addition to angiotensin II, in the pathogenesis of hypertension and renal diseases. Beneficial effects of mineralocorticoid receptor (MR) blockers against these diseases have been reported and are independent of the effects exerted by renin-angiotensin system (RAS) inhibitors. MR blockers are increasingly being used, not only for primary aldosteronism but also for other resistant hypertensive patients whose blood pressure is insufficiently controlled by RAS inhibitors. In these settings, MR blockers have shown impressive results. In addition, anti-proteinuric effects of MR blockers have been observed in hypertensive patients treated with RAS inhibitors, but without significant effects on blood pressure. Interestingly, these effects of MR blockers are not always dependent on plasma aldosterone levels. These data suggest that MR blockers provide a potential therapeutic approach for patients with hypertension and renal impairment who are being treated with RAS inhibitors.