Document Detail

Release of preformed Ang II from myocytes mediates angiotensinogen and ET-1 gene overexpression in vivo via AT1 receptor.
MedLine Citation:
PMID:  12431448     Owner:  NLM     Status:  MEDLINE    
The role of angiotensin II in pressure overload is still debated because notwithstanding its effects on myocyte contractility angiotensin II is not an obligatory factor for the development of hypertrophy. To define the role of angiotensin II in acute pressure overload we studied the effects of AT1 blockade (valsartan 80mg per day) on myocardial contractility, cardiac growth factor gene expression, and myocardial hypertrophy in aortic banded (60mmHg) pigs. Acute pressure overload caused an abrupt reduction of myocardial contractility, measured by the end-systolic stiffness constant, and a sharp increase in end-systolic stress which rapidly normalized (within 12h) in the placebo group. In AT1-blocked animals end-systolic stiffness constant remained significantly depressed up to 24h and end-systolic stress was still elevated up to 48h (both P<0.05 vs placebo). In both groups confocal microscopy revealed that granular staining of angiotensin II in cardiomyocyte cytoplasm disappeared after 30min of pressure overload. AT1 blockade abolished following cardiac overexpression of angiotensinogen and endothelin-1 genes as shown in RT-PCR studies and the consequent angiotensin II and endothelin-1 release in the coronary circulation. Conversely, insulin-like growth factor-I and ACE mRNA overexpression, as well as the onset of left ventricular mass increase, were not significantly affected by AT1 blockade. In conclusion: (1) mechanical stress releases preformed angiotensin II from myocyte in vivo; (2) the AT1 blockade abolishes cardiac angiotensin II and endothelin-1 production with delayed recovery of myocardial contractility; whereas (3) the overexpression of insulin-like growth factor-I gene and the development of myocardial hypertrophy are not angiotensin II-mediated effects.
Pietro Amedeo Modesti; Sra Zecchi-Orlandini; Simone Vanni; Gianluca Polidori; Iacopo Bertolozzi; Avio Maria Perna; Lucia Formigli; Ilaria Cecioni; Mirella Coppo; Maria Boddi; Gian Gastone Neri Serneri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  34     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-14     Completed Date:  2003-06-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1491-500     Citation Subset:  IM    
Clinica Medica Generale e Cardiologia, University of Florence, Viale Morgagni 85, 50134, Florence, Italy.
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MeSH Terms
Angiotensin II / secretion*
Angiotensinogen / biosynthesis*,  genetics
Aortic Valve Stenosis / physiopathology
Cytoplasm / chemistry
Disease Models, Animal
Endothelin-1 / biosynthesis*,  genetics
Gene Expression Regulation*
Heart / secretion*
Heart Catheterization
Insulin-Like Growth Factor I / biosynthesis,  genetics
Microscopy, Confocal
Myocardium / cytology,  metabolism*
RNA, Messenger / biosynthesis,  genetics
Receptor, Angiotensin, Type 1
Receptors, Angiotensin / antagonists & inhibitors,  physiology*
Renin-Angiotensin System / physiology
Stress, Mechanical
Tetrazoles / pharmacology
Valine / analogs & derivatives*,  pharmacology
Reg. No./Substance:
0/Endothelin-1; 0/RNA, Messenger; 0/Receptor, Angiotensin, Type 1; 0/Receptors, Angiotensin; 0/Tetrazoles; 11002-13-4/Angiotensinogen; 11128-99-7/Angiotensin II; 137862-53-4/valsartan; 67763-96-6/Insulin-Like Growth Factor I; 7004-03-7/Valine

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

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