Published online before print September 17, 2007, doi: 10.1161/HYPERTENSIONAHA.107.098699
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(Hypertension. 2007;50:842.)
© 2007 American Heart Association, Inc.
Editorial Commentaries |
Avoiding Vicious Circles
Mineralocorticoid Receptor Antagonism Prevents Vascular Oxidative Stress Early After Myocardial Infarction
From the Institut für Kardiovaskuläre Physiologie, Fachbereich Medizin, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Correspondence to Ralf P. Brandes, Institut für Kardiovaskuläre Physiologie, Fachbereich Medizin, Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany. E-mail r.brandes@em.uni-frankfurt.de
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Oxidative stress is thought to play a key role in the initiation and progression of cardiovascular diseases. Increased formation of reactive oxygen species (ROS) leads to endothelial dysfunction through the breakdown of NO, promotes proinflammatory gene expression, and increases the sympathetic tone. A multitude of stimuli including inflammation, cardiovascular risk factors like hypertension and cigarette smoke as well as a broad spectrum of hormones increase the systemic oxidative stress. Among these elements, however, angiotensin II is probably the most robust stimulus for ROS, which derive from Nox1- and Nox2-containing NADPH oxidases. In fact, angiotensin II activates and induces these ROS-generating enzymes.
Angiotensin II is also the classic stimulus for the release of aldosterone. Interestingly, also aldosterone is an independent stimulus for vascular ROS production. This steroid hormone induces components of the NADPH oxidase like p47phox1 and p22phox and acutely increases ROS production in vascular cells2 probably through EGF receptor transactivation. Importantly, ROS may be mandatory for the deleterious effects of aldosterone in the cardiovascular system: for example, genetic deletion of the Nox2-containing NADPH oxidases prevents the aldosterone-induced interstitial fibrosis in the mouse heart.3 Furthermore, antioxidants prevent the aldosterone-induced expression of intercellular adhesion molecule-1 and MCP-1 as well as tumor necrosis factor 
in the rat heart.4
On such a basis it is possible that blockade of the mineralocorticoid receptor by either spironolactone or the more specific aldosterone antagonist eplerenone is beneficial for vascular function in situations of increased aldosterone formation such as chronic congestive heart failure5 or experimental application of angiotensin
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