Aldosterone: clinical implications in essential hypertension

ABSTRACT

The blockade of renin-angiotensin-aldosterone system with ACE inhibitors or angiotensin receptor antagonists has resulted in beneficial effects in essential hypertensive patients. However, occurrence of cardiovascular events has not been appropriately controlled beyond a certain percentage. One reason could be the pathophysiological effects of aldosterone, the final component of the system. The aldosterone escape phenomenon could explain undesirable outcomes observed in hypertensive patients even under treatment with ACE inhibitors or angiotensin antagonists. Aldosterone has direct effects on the vasculature, the heart and the kidney. Aldosterone has been associated with vascular smooth muscle cell hypertrophy, endothelial dysfunction, cardiac fibrosis, proteinuria and renal vascular injury. Animal models and clinical trials have proven the benefit of aldosterone receptor antagonism. Even in small doses, spironolactone was able to attenuate proteinuria and reduce death and morbidity among heart failure patients. The potential advantage eplerenone, the first drug of a new class - selective aldosterone receptor antagonists - lies on a very low incidence of side effects, although clinical studies are still necessary to confirm efficacy, tolerability and safety. In conclusion, aldosterone antagonism must be considered in hypertensive patients presenting heart failure or proteinuria and in those with resistant hypertension. With the increased recognition hyperaldosteronism in "essential" hypertension, the use such drugs may become more widespread.