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  • Open Access

The good and the ugly: ANP antagonizes the deleterious effects of aldosterone in hypertensive cardiac remodeling

  • 1Email author,
  • 1,
  • 1,
  • 1,
  • 2,
  • 2,
  • 3,
  • 2 and
  • 1
BMC Pharmacology and Toxicology201314 (Suppl 1) :P46

  • Published:


  • Aldosterone
  • Atrial Natriuretic Peptide
  • Mineralocorticoid Receptor
  • Cardiac Remodel
  • Eplerenone


Atrial natriuretic peptide (ANP), via its guanylyl cyclase A (GC-A) receptor and cyclic GMP formation, exerts cardiac antihypertrophic and antifibrotic actions. Conversely, aldosterone promotes pathological cardiac remodeling via the mineralocorticoid receptor (MR). To investigate whether local cardiac ANP/GC-A signaling counteracts the effects of aldosterone during experimental hypertensive cardiac remodeling.


We studied the impact of the MR antagonist eplerenone (100 mg/kg/day) on cardiac remodeling after transverse aortic constriction (TAC) in mice with conditional, cardiomyocyte-restricted deletion of GC-A (CM GC-A KO) [1] or cGMP-dependent protein kinase I (CM cGK I KO) [2] and respective controls (n=10 in each group). Left ventricular (LV) hypertrophy and interstitial fibrosis were significantly exacerbated in both CM GC-A KO and cGK I KO mice after TAC. These histological changes were accompanied by decreased LV SERCA2a expression, increased CTGF and LV dilatation together with contractile dysfunction. Eplerenone had no effect on systemic blood pressure but fully prevented these pressure-overload induced cardiac morphological, molecular and functional alterations in both CM GC-A KO and CM cGK I KO mice. However, eplerenone did not inhibit TAC-induced MAPK ERK1/2 phosphorylation/activation, suggesting that the non-genomic effects of aldosterone are not involved in exacerbated hypertensive cardiac remodeling of the KO mice. Intriguingly, in transfected HEK 293 cells, ANP inhibited the aldosterone-induced nuclear translocation of the MR.


ANP, via GC-A/cGMP/cGKI signaling in cardiac myocytes, attenuates hypertensive cardiac remodeling and dysfunction. These protective ANP effects seem to be mediated at least in part by counterregulation of the deleterious genomic (MR-mediated) cardiac actions of aldosterone.



Supported by the comprehensive heart failure center (CHCF) in Würzburg. The CM cGKI KO mice were generated together with Dr. Franz Hofmann and Dr. Robert Feil.

Authors’ Affiliations

Institute of Physiology, University of Würzburg, Germany
Department of Internal Medicine 1, University Hospital Würzburg, Germany
Department of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg- Essen, Germany


  1. Holtwick R, van Eickels M, Skryabin BV, Baba HA, Bubikat A, Begrow F, Schneider MD, Garbers DL, Kuhn M: Pressure-independent cardiac hypertrophy in mice with cardiomyocyte-restricted inactivation of the atrial natriuretic peptide receptor guanyl cyclase-A. J Clin Invest. 2003, 111: 1399-1407.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Frantz S, Klaiber M, Baba HA, Oberwinkler H, Völker K, Gaβner B, Bayer B, Abeβer M, Schuh K, Feil R, Hofmann F, Kuhn M: Stress-dependent dilated cardiomyopathy in mice with cardiomyocyte-restricted inactivation of cyclic GMP-dependent protein kinase I. Eur Heart J. 2013, 34: 1233-1244. 10.1093/eurheartj/ehr445.PubMed CentralView ArticlePubMedGoogle Scholar


© Nakagawa et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.