Skip to main content


  • Meeting abstract
  • Open Access

cGMP and cardiac hypertrophy

  • 1, 2,
  • 1,
  • 2,
  • 2,
  • 2 and
  • 1Email author
BMC Pharmacology and Toxicology201516 (Suppl 1) :A12

  • Published:


  • Cardiac Hypertrophy
  • Atrial Natriuretic Peptide
  • Cardiac Contractility
  • Transverse Aortic Constriction
  • Hypertrophied Heart


cGMP as a second messenger regulates cardiac contractility and might protect the heart from hypertrophy and failure by acting in distinct subcellular microdomains. However, direct visualization of cGMP in subcellular microdomains of adult cardiomyocytes has been challenging. Little is known also about changes in cardiomyocyte cGMP signalling at an early stage of the disease.


We used a highly sensitive cytosolic and membrane-targeted Förster resonance energy transfer (FRET)-based biosensors for cGMP and cAMP for real time measurements in freshly isolated sensor-trasngenic adult ventricular cardiomyocytes. Combined with single cell contractility measurements, biochemical techniques and whole-heart recording, the effect of atrial natriuretic peptide (ANP) on cardiomyocyte cGMP/cAMP and contractility in healthy and hypertrophied hearts (after transverse aortic constriction).


Contractility measurements in hypertrophied hearts have unravelled ANP-induced augmentation of catecholamine stimulated increase in force and frequency of contraction which was present only in diseased hearts at the state of early compensated cardiac hypertrophy. Interestingly, this effect was not due to changes in cGMP content, membrane receptor densities or whole-cells phosphodiesterase (PDE) activity. Instead, physical redistribution of the cGMP-stimulated PDE2 and cGMP-inhibited PDE3 between distinct membrane domains led to a change of cAMP compartmentation towards an ANP/cGMP/PDE3-dependent increase of local cAMP levels in a microdomain regulating cardiac contractility [1]. FRET-based cGMP measurements revealed relatively small increase of cGMP upon ANP stimulation [2], stringent compartmentation of ANP/cGMP signals to T-tubular membranes and apparent absence of receptor desensitization in early cardiac hypertrophy [1].


ANP/cGMP signalling can play distinct roles in cardiac disease, including a previously unrecognized contractility augmentation in early hypertrophy which might support heart function upon pressure overload. This can be achieved by PDE2/3 redistribution-dependent changes in cGMP/cAMP compartmentation.

Authors’ Affiliations

Institute for Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf (UKE), D-22529 Hamburg, Germany
Heart Research Center Göttingen, University of Göttingen Medical Center (UMG), Göttingen, Germany


  1. Perera RK, et al: Microdomain switch of cGMP-regulated phosphodiesterases leads to ANP-induced augmentation of β-adrenoceptor-stimulated contractility in early cardiac hypertrophy. Circ Res. 2015, 116: 1304-1311. 10.1161/CIRCRESAHA.116.306082.View ArticlePubMedGoogle Scholar
  2. Götz KR, et al: Transgenic mice for real-time visualization of cGMP in intact adult cardiomyocytes. Circ Res. 2014, 114: 1235-1245. 10.1161/CIRCRESAHA.114.302437.View ArticlePubMedGoogle Scholar


© Perera and Subramanian et al. 2015

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. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.