Published online before print June 11, 2007, doi: 10.1161/HYPERTENSIONAHA.107.092437
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2007;50:297.)
© 2007 American Heart Association, Inc.
Editorial Commentaries |
Estrogen Receptor Activation—Good, Aldosterone Receptor Blockade—Beneficial, Communication Between Receptors...Priceless
From the Cleveland Clinic, Pepper Pike, Ohio.
Correspondence to John C. Barbato, Cleveland Clinic, 29426 Gates Mills Blvd, Pepper Pike, OH 44124. E-mail jcb-pad@sbcglobal.net
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Steroid receptors are essentially transcription factors. When estrogens activate estrogen receptors (ERs) and aldosterone activates the mineralocorticoid receptor (MR) these steroid-receptor complexes enter the nucleus. On entry, these complexes bind to their respective response elements leading to the regulation of gene expression. This transcriptional regulation of key genes in target tissues yields relevant reproductive and endocrine functions. Because ER and MR are expressed in cardiac myocytes, fibroblasts, and vascular cells, genes essential to cardiovascular function and cardiovascular pathophysiology are regulated by aldosterone and estrogens.1,2
The consensus from research on cardiovascular tissue focusing on estrogens is that ER activation is beneficial. Specifically, ER activation has been suggested to attenuate mitogen-activated protein kinase growth signaling in response to pressure overload, increase endothelial NO synthesis, reduce vascular cell proliferation, and decrease endothelin expression.1 In addition, blunted hypertrophic responses in female mice lacking the ryanodine receptor-associated protein and guanylyl cyclase-A receptor suggest that estrogens may attenuate calcineurin/nuclear factor-activated T-cell signaling and or mediate downstream signaling in the atrial natriuretic peptide-guanylyl cyclase cascade.3,4 Whereas ER activation with specific and nonspecific estrogen agonists produce molecular responses favoring cardiovascular protection, the contrary has been demonstrated with studies examining MR activation.2
The deleterious nature of excessive MR activation was evidenced by the Randomized Aldactone Evaluation Study.2 The Randomized Aldactone Evaluation Study demonstrated improved outcomes in patients with heart failure being treated with the MR antagonist spironolactone. The rationale for the use of spironolactone in heart failure was based on the ability of aldosterone, via the genomic pathway, to
Related Article:
and ß, Attenuate Cardiovascular Remodeling in Aldosterone Salt–Treated Rats
Hypertension 2007 50: 432-438.