Published online before print June 30, 2008, doi: 10.1161/HYPERTENSIONAHA.108.115733
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2008;52:209.)
© 2008 American Heart Association, Inc.
Editorial Commentaries |
Cardiac Benefits of Mineralocorticoid Receptor Inhibition in Renal Failure
From the Department of Medicine/Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany.
Correspondence to Kristof Graf, Department of Medicine/Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. E-mail graf@dhzb.de
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Large clinical trials have demonstrated profound benefits of aldosterone inhibition by spironolactone in patients with heart failure (impaired left ventricle function <40%) and with eplerenone in patients with myocardial infarction.1 The key enzyme in aldosterone production is aldosterone synthase (CYP11B2). CYP11B2 is predominantly expressed in the adrenal gland but is also expressed in the cardiovascular system. Angiotensin (Ang) II is the major stimulus for CYP11B2-related aldosterone synthesis. Preclinical and clinical studies have shown that Ang II inhibition is pivotal to the treatment of heart failure and ischemic heart disease. The previous belief was that inhibition of Ang II should be sufficient to block aldosterone production; however, aldosterone levels can be elevated although Ang II production is inhibited or its action is blocked. This state of affairs is called the aldosterone breakthrough phenomenon; its mechanisms are unclear.2 Indeed, additional inhibition of the mineralocorticoid receptor (MR) reduces proteinuria in Ang-converting enzyme inhibitor–treated patients with early diabetic nephropathy.3
The strong effect of aldosterone on inflammation in the cardiovascular system has been reviewed recently.4 MR antagonism prevents vascular injury and cardiac fibrosis, activation of activator protein-1 and nuclear factor 
B, and upregulation of the basic fibroblast growth factor in hearts of rats doubly transgenic for the human renin and angiotensinogen genes. MR antagonism decreases aortic inflammation, fibrosis, and hypertrophy in hypertensive rats. Like Ang II, aldosterone activates reduced nicotinamide-adenine dinucleotide phosphate oxidases in the rat and increases expression of the reduced nicotinamide-adenine dinucleotide phosphate oxidase subunit p22phox in human monocytes.5
The present study by
Related Article:
Hypertension 2008 52: 295-300.