Published online before print June 5, 2006, doi: 10.1161/01.HYP.0000226055.65364.8e
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(Hypertension. 2006;48:27.)
© 2006 American Heart Association, Inc.
Editorial Commentaries |
Endothelial NO Synthase Target of Aldosterone
From the Medizinische Klinik I, Universitätsklinikum, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Correspondence to Johann Bauersachs, Medizinische Klinik I, Universitätsklinikum, Josef-Schneider-Str 2, D-97080 Würzburg, Germany. E-mail j.bauersachs@medizin.uni-wuerzburg.de
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The mineralocorticoid hormone aldosterone plays a pivotal role in sodium resorption and potassium excretion and, consequently, in fluid balance and blood pressure homeostasis.1 Current studies indicate that mineralocorticoid receptors are present not only in epithelial cells, and aldosterone also acts on nonepithelial tissues, including the heart, blood vessels, and brain. In the vascular system, mineralocorticoid receptors and the enzyme 11-ß-hydroxy-steroid dehydrogenase type 2, which confers aldosterone specificity to the mineralocorticoid receptor, could be localized in endothelial and vascular smooth muscle cells.2 Other than the mineralocorticoid receptor, steroidogenic enzymes necessary to synthesize aldosterone are also expressed in extra-adrenal tissues, including the vascular wall, which, although still controversial, may be consistent with de novo aldosterone production acting in an autocrine/paracrine fashion.
Aldosterone induces oxidative stress in vascular cells through NADPH oxidase activation, which plays a central role for endothelial dysfunction and atherosclerotic vascular disease.3 Mineralocorticoid receptor blockade increased NO bioavailability and improved impaired endothelial function by decreasing oxidative stress in hypertension, atherosclerosis, and heart failure.3–5 In a rat model of heart failure, aldosterone antagonism reduced vascular superoxide anion formation, and in combination with an angiotensin-converting enzyme inhibitor, increased the expression of the endothelial NO synthase (eNOS) and restored the attenuated NO-mediated relaxation.5
In the current issue of Hypertension, Nagata et al6 report that treatment of cultured human endothelial cells with aldosterone results in the enhanced generation of reactive oxygen species through activation of NADPH oxidase, mainly via enhanced transcription of the subunit p47phox and translocation to the membrane. Most importantly, the
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