Basic Research in Cardiology

, Volume 106, Issue 4, pp 591–602 | Cite as

Chronic cardiac pressure overload induces adrenal medulla hypertrophy and increased catecholamine synthesis

  • Johanna Schneider
  • Achim Lother
  • Lutz Hein
  • Ralf GilsbachEmail author
Original Contribution


Increased activity of the sympathetic system is an important feature contributing to the pathogenesis and progression of chronic heart failure. While the mechanisms and consequences of enhanced norepinephrine release from sympathetic nerves have been intensely studied, the role of the adrenal gland in the development of cardiac hypertrophy and progression of heart failure is less well known. Thus, the aim of the present study was to determine the effect of chronic cardiac pressure overload in mice on adrenal medulla structure and function. Cardiac hypertrophy was induced in wild-type mice by transverse aortic constriction (TAC) for 8 weeks. After TAC, the degree of cardiac hypertrophy correlated significantly with adrenal weight and adrenal catecholamine storage. In the medulla, TAC caused an increase in chromaffin cell size but did not result in chromaffin cell proliferation. Ablation of chromaffin α2C-adrenoceptors did not affect adrenal weight or epinephrine synthesis. However, unilateral denervation of the adrenal gland completely prevented adrenal hypertrophy and increased catecholamine synthesis. Transcriptome analysis of microdissected adrenal medulla identified 483 up- and 231 downregulated, well-annotated genes after TAC. Among these genes, G protein-coupled receptor kinases 2 (Grk2) and 6 and phenylethanolamine N-methyltransferase (Pnmt) were significantly upregulated by TAC. In vitro, acetylcholine-induced Pnmt and Grk2 expression as well as enhanced epinephrine content was prevented by inhibition of nicotinic acetylcholine receptors and Ca2+/calmodulin-dependent signaling. Thus, activation of preganglionic sympathetic nerves innervating the adrenal medulla plays an essential role in inducing adrenal hypertrophy, enhanced catecholamine synthesis and induction of Grk2 expression after cardiac pressure overload.


Adrenal medulla Epinephrine Sympathetic nervous system Heart failure 



This study was supported by the Deutsche Forschungsgemeinschaft (DFG He 2073/3-1). We thank the EMBL GeneCore (Heidelberg, Germany) staff, especially Vladimir Benes and Tomi Ivacevic, for performing the Affymetrix microarray experiments.

Supplementary material

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Supplementary material 1 (DOC 4.19 mb)
395_2011_166_MOESM2_ESM.pdf (185 kb)
Supplementary material 2 (PDF 185 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Johanna Schneider
    • 1
  • Achim Lother
    • 1
  • Lutz Hein
    • 1
    • 2
  • Ralf Gilsbach
    • 1
    Email author
  1. 1.Institute of Experimental and Clinical Pharmacology and ToxicologyUniversity of FreiburgFreiburgGermany
  2. 2.BIOSS Centre for Biological Signalling StudiesUniversity of FreiburgFreiburgGermany

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