Aldosterone synthase inhibitors: pharmacological and clinical aspects.
Aldosterone plays an important pathophysiological role in cardiovascular disease, and aldosterone (mineralocorticoid) receptor antagonism has been used in the treatment of heart failure and hypertension. However, aldosterone receptor antagonism is associated with an increase in plasma aldosterone levels, which may result in non-mineralocorticoid receptor-mediated (non-genomic) adverse effects. Therefore, the inhibition of aldosterone synthesis may be preferable to blockade at the receptor level. Direct inhibitors of aldosterone synthase are currently under development. However, specificity for aldosterone synthase remains a challenge, and the search for more potent and more selective compounds is ongoing. Experimental animal and human studies are required to establish whether aldosterone synthase inhibitors will be successful as therapeutic agents.
Jansen
Pieter M
PM
Erasmus MC, Division of Pharmacology, Vascular & Metabolic Diseases, Department of Internal Medicine, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands.
van den Meiracker
Anton H
AH
Jan Danser
A H
AH