Aldosterone, a specific
mineralocorticoid receptor (MR) agonist and a key player in the development of
hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system.
Hypertension can be generally treated by negating the effects of
angiotensin II through the use of
angiotensin-converting enzyme inhibitors (ACE-Is) or
angiotensin II type 1 receptor antagonists (ARBs). However, the efficacy of
angiotensin II blockade by such drugs is sometimes diminished by the so-called "
aldosterone breakthrough" effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS) inhibitors) gradually lose their effectiveness against
hypertension due to the overproduction of
aldosterone, known as primary
aldosteronism. Although MR antagonists are used to antagonize the effects of
aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as
hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some
dihydropyridine Ca(2+) channel blockers (CCBs) have inhibitory actions on
aldosterone production in in vitro and in the clinical setting. Therefore, the use of such
dihydropyridine CCBs to treat
aldosterone-related
hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism of action of CCBs on
aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.