Aldosterone synthase inhibition: cardiorenal protection in animal disease models and translation of hormonal effects to human subjects

• Published in: Journal of translational medicine Vol. 12; no. 1; p. 340
• Main Authors: Ménard, Joël, Rigel, Dean F, Watson, Catherine, Jeng, Arco Y, Fu, Fumin, Beil, Michael, Liu, Jing, Chen, Wei, Hu, Chii-Whei, Leung-Chu, Jennifer, LaSala, Daniel, Liang, Guiqing, Rebello, Sam, Zhang, Yiming, Dole, William P
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.12.2014; BioMed Central
• Subjects: Adrenal glands; Aldosterone; Analysis; Angiotensinogen - physiology; Animal diseases; Animals; Biomedical research; Comparative analysis; Corticosteroids; Cytochrome P-450 CYP11B2 - antagonists & inhibitors; Disease Models, Animal; Double-Blind Method; Enzymes; Eplerenone; Experiments; Haplorhini; Health aspects; Heart - drug effects; Heart - physiopathology; Humans; Hypertension; Imidazoles - pharmacology; Kidney - drug effects; Kidney - physiopathology; Laboratory animals; Life Sciences; Male; Monkeys & apes; Placebos; Plasma; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Renin - physiology; Rodents; Santé publique et épidémiologie; Spironolactone - analogs & derivatives; Spironolactone - pharmacology; Studies; Translational Medical Research; Germany; Double-transgenic rat; Translational research; Eplerenone; Mineralocorticoid; Cushing ’ s disease; Cortisol; Aldosterone

Aldosterone synthase inhibition provides the potential to attenuate both the mineralocorticoid receptor-dependent and independent actions of aldosterone. In vitro studies with recombinant human enzymes showed LCI699 to be a potent, reversible, competitive inhibitor of aldosterone synthase (K i = 1.4...