| Chronic cardiac pressure overload induces adrenal medulla hypertrophy and increased catecholamine synthesis. | |
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MedLine Citation:
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PMID: 21547520 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Johanna Schneider; Achim Lother; Lutz Hein; Ralf Gilsbach |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-03-10 |
Journal Detail:
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Title: Basic research in cardiology Volume: 106 ISSN: 1435-1803 ISO Abbreviation: Basic Res. Cardiol. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-01 Completed Date: 2011-10-03 Revised Date: 2012-06-07 |
Medline Journal Info:
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Nlm Unique ID: 0360342 Medline TA: Basic Res Cardiol Country: Germany |
Other Details:
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Languages: eng Pagination: 591-602 Citation Subset: IM |
Affiliation:
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Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, Freiburg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenal Glands
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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:
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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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