Aldosterone synthase inhibitors in cardiovascular and renal diseases.
Aldosterone is involved in various cardiovascular pathologies, including hypertension, heart failure, atherosclerosis and fibrosis. Mineralocorticoid receptor (MR)-dependent and -independent, genomic and non-genomic processes mediate its complex effects. Spironolactone and eplerenone, both MR antagonists, are the only commercially available compounds targeting directly the actions of aldosterone. However, due to the poor selectivity (spironolactone), low potency (eplerenone) and the fact that only MR-dependent effects of aldosterone can be inhibited, these drugs have limited clinical use. An attractive approach to abolish potentially all of aldosterone-mediated pathologies is the inhibition of aldosterone synthase. This review summarizes current knowledge on the complex effects mediated by aldosterone, potential advantages and disadvantages of aldosterone inhibition and novel directions in the development of aldosterone synthase inhibitors.
CARIM-School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
Pawel
P
Namsolleck
Thomas
T
Unger
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology; D019405:Cytochrome P-450 CYP11B2 / Q000037:antagonists & inhibitors*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000201:enzymology; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*
D000451:Mineralocorticoid Receptor Antagonists; D019405:Cytochrome P-450 CYP11B2
aldosterone synthase inhibitors; fibrosis; inflammation; mineralocorticoid receptor; oxidative stress