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(Circulation Research. 2005;96:610.)
© 2005 American Heart Association, Inc.

Editorials

Angiotensin II: A Devious Activator of Mineralocorticoid Receptor-Dependent Gene Expression

Burns C. Blaxall, Joseph M. Miano, Bradford C. Berk

From the Cardiovascular Research Institute, and the Department of Medicine, University of Rochester, NY

Correspondence to Bradford C. Berk, University of Rochester, Cardiovascular Research Institute, 601 Elmwood Ave, Box 679, Rochester, NY 14642. E-mail Bradford_Berk@URMC.rochester.edu

See related article, pages 643–650

Key Words: angiotensin II • mineralocorticoid receptor • aldosterone • spironolactone

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In this issue of Circulation Research Jaffe and Mendelsohn¹ show that angiotensin II (Ang II) directly activates the mineralocorticoid receptor (MR). Using cultured human coronary and aortic vascular smooth muscle cells (VSMC) they show strong evidence for expression of both the MR and the cortisol inactivating enzyme 11-ß-hydroxysteroid-dehydrogenase-2 necessary for mineralocorticoid action. Importantly they show that Ang II activation of MR is independent of aldosterone generation by VSMC, suggesting a direct effect. Finally they used microarray analysis to define genes induced by aldosterone-dependent MR transcription. The microarray results yielded an "All Star" parade of candidates for vascular aging as they included genes involved in vascular fibrosis, inflammation and calcification. These data provide further support for the evolving role of the MR as a signal effector for Ang II and provide a new MR-dependent mechanism by which Ang II promotes cardiovascular disease.

The links between Ang II and aldosterone have become increasingly numerous over the past 10 years. Because Ang II stimulates the synthesis and release of aldosterone, it has been suggested that vascular effects of Ang II are mediated in part by aldosterone. Support for this concept includes findings that Ang II receptors are up-regulated by aldosterone,² data that spironolactone decreased cardiac hypertrophy, inflammation and fibrosis induced by Ang II,³ and evidence that Ang II-mediated oxidative stress, endothelial dysfunction, and resistance artery structural remodeling were blocked by spironolactone.⁴ However, it was believed that these effects were mediated by MR activation via either aldosterone produced in the adrenal cortex or locally . . . [Full Text of this Article]

Related Article:

Angiotensin II and Aldosterone Regulate Gene Transcription Via Functional Mineralocortocoid Receptors in Human Coronary Artery Smooth Muscle Cells

Iris Z. Jaffe and Michael E. Mendelsohn
Circ. Res. 2005 96: 643-650. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				E. L. Schiffrin Effects of Aldosterone on the Vasculature Hypertension, March 1, 2006; 47(3): 312 - 318. [Full Text] [PDF]