Aldosterone receptor antagonists: Biology and novel therapeutic applications

Abstract

A dysregulation of the aldosterone system has been involved in the pathophysiology of cardiovascular diseases, including myocardial failure and, partially, essential hypertension. In humans and in rat models, aldosterone action induces heart remodeling and interstitial and perivascular myocardial fibrosis. Therefore, a rationale for using aldosterone antagonists (ARAs) of the spironolactone family, which have been available for decades for the treatment of aldosterone excess syndromes, has now emerged. The development of compounds such as eplerenone, with a greater selectivity for mineralocorticoid receptors, is promising also in terms of reduction of endocrine side effects. The use of ARAs for the treatment of myocardial failure and selected cases of hypertension, in combination with the current therapy, has been strongly supported by trials such as the Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Neurohormonal Efficacy and Survival Study (EPHESUS). Thus, the addition of ARAs to the conventional therapy appears beneficial, leading to an improved survival rate and a reduced incidence of cardiac complications.

Pleiotropic Effect of Aldosterone on Human Endothelial Cells In Vitro

“…Eplerenone was significantly less effective than aldosterone in inhibiting HBMEC proliferation and the agonist completely reversed the statistically insignificant inhibition observed with the antagonist alone. Aldactone was again more potent than eplerenone (not shown) possibly due to its affinity for various classes of steroid receptors [24].…”

Consenso de la Sociedad Latinoamericana de Nefrología e Hipertensión en relación con el papel de los antagonistas del receptor mineralocorticoide en enfermedad renal crónica

“…La aldosterona es uno de los componentes del SRAA, secretado por la zona glomerulosa suprarrenal bajo el estímulo, principalmente, de la angiotensina II y en presencia de hiperpotasemia 18 . La depleción de volumen y la liberación de corticotropina son otros estímulos para la liberación de aldosterona 19 . La aldosterona se une al RM que se expresa ampliamente en varios segmentos del riñón, como el túbulo contorneado distal, el túbulo conector y el túbulo colector cortical, donde estimula la reabsorción de Na + y la excreción de K + .…”