Document Detail


Chronic cardiac pressure overload induces adrenal medulla hypertrophy and increased catecholamine synthesis.
MedLine Citation:
PMID:  21547520     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 α(2C)-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 Ca(2+)/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.
Authors:
Johanna Schneider; Achim Lother; Lutz Hein; Ralf Gilsbach
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-10
Journal Detail:
Title:  Basic research in cardiology     Volume:  106     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-01     Completed Date:  2011-10-03     Revised Date:  2012-06-07    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  591-602     Citation Subset:  IM    
Affiliation:
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, Freiburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adrenal Glands / innervation
Adrenal Medulla / pathology*
Animals
Blood Pressure
Denervation
Epinephrine / biosynthesis*
G-Protein-Coupled Receptor Kinase 2 / genetics
Gene Expression Profiling
Hypertrophy
Male
Mice
Mice, Inbred C57BL
RNA, Messenger / analysis
Receptors, Adrenergic, alpha-2 / physiology
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Receptors, Adrenergic, alpha-2; 51-43-4/Epinephrine; EC 2.7.11.15/Adrbk1 protein, mouse; EC 2.7.11.15/G-Protein-Coupled Receptor Kinase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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