Document Detail

Angiotensin receptor blockade improves the net balance of cardiac Ca(2+) handling-related proteins in sympathetic hyperactivity-induced heart failure.
MedLine Citation:
PMID:  21277865     Owner:  NLM     Status:  Publisher    
AIMS: The clinical benefits of angiotensin II type 1 (AT1) receptor blockers (ARB) in heart failure (HF) include cardiac anti-remodeling and improved ventricular function. However, the cellular mechanisms underlying the benefits of ARB on ventricular function need to be better clarified. In the present manuscript, we evaluated the effects of AT1 receptor blockade on the net balance of Ca(2+) handling proteins in hearts of mice lacking α(2A) and α(2C) adrenoceptors (α(2A)/α(2C)ARKO), which develop sympathetic hyperactivity (SH) induced- HF. MAIN METHODS: A cohort of male wild-type (WT) and congenic α(2A)/α(2C)ARKO mice in a C57BL6/J genetic background (5-7 mo of age) was randomly assigned to receive either placebo or ARB (Losartan, 10mg/kg for 8wks). Ventricular function (VF) was assessed by echocardiography, and cardiac myocyte width and ventricular fibrosis by a computer-assisted morphometric system. Sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), phospholamban (PLN), phospho-Ser(16)-PLN, phospho-Thr(17)-PLN, phosphatase 1 (PP1), Na(+)-Ca(2+) exchanger (NCX), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and phospho-Thr(286)-CaMKII were analyzed by Western blot. KEY FINDINGS: α(2A)/α(2C)ARKO mice displayed ventricular dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis paralleled by decreased SERCA2 and increased phospho-Thr(17)-PLN, CaMKII, phospho-Thr(286)-CaMKII and NCX levels. ARB induced anti-cardiac remodeling effect and improved VF in α(2A)/α(2C)ARKO associated with increased SERCA2 and phospho-Ser(16)-PLN levels, and SERCA2:NCX ratio. Additionally, ARB decreased phospho-Thr(17)-PLN levels as well as reestablished NCX, CaMKII and phospho-Thr(286)-CaMKII toward WT levels. SIGNIFICANCE: Altogether, these data provide new insights on intracellular Ca(2+) regulatory mechanisms underlying improved ventricular function by ARB therapy in HF.
Julio C B Ferreira; Jose B N Moreira; Juliane C Campos; Marcelo G Pereira; Katt C Mattos; Marcele A Coelho; Patricia C Brum
Related Documents :
21277865 - Angiotensin receptor blockade improves the net balance of cardiac ca(2+) handling-relat...
8914885 - High-dose streptokinase therapy with three million units in one hour significantly impr...
7691765 - Effects of magnesium infusion on thrombolytic and non-thrombolytic treated patients wit...
4252395 - Enzymatic and immunochemical determination of plasminogen and plasmin in different phys...
6701705 - Primary cardiac hydatid disease. a case report.
24462345 - Role of cardiac sympathetic nerves in preventing orthostatic hypotension in parkinson's...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-25
Journal Detail:
Title:  Life sciences     Volume:  -     ISSN:  1879-0631     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010. Published by Elsevier Inc.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

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

Previous Document:  Endogenous cannabinoid receptor agonist anandamide induces peripheral antinociception by activation ...
Next Document:  Expression of the IgSF protein Kirre in the rat central nervous system.