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Stimulation of cardiac apoptosis in ovariectomized hypertensive rats: potential role of the renin-angiotensin system.
MedLine Citation:
PMID:  21107282     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
OBJECTIVES: The mechanisms underlying the increased cardiovascular risk after menopause are poorly understood. Estrogens modulate the cardiac renin-angiotensin system (RAS) and influence cardiac adaptation to afterload. To investigate whether the loss of the natural inhibition of the RAS by estrogen may be linked to an increase of cardiac apoptosis, we studied 17β-estradiol (E2) and/or angiotensin-converting enzyme (ACE) inhibitor treatment effects on cardiomyocyte survival in ovariectomized spontaneously hypertensive rats (SHRs).
METHODS: Five groups of female SHRs were evaluated for 8 weeks. One group served as nonovariectomized control; the other four groups underwent bilateral ovariectomy and were randomized to receive 60-day-release pellets containing placebo or 0.5 mg of E2, the ACE inhibitor ramipril at the dosage of 2.5 mg/kg per day, or the combination of the two treatments.
RESULTS: Ovariectomy increased cardiomyocyte apoptosis and induced proapoptotic changes of Bcl-2 and Bax genes and proteins. These modifications were associated with an upregulation of ACE and angiotensin II type 1 (AT1) receptor genes. Ramipril was as effective as E2 in preventing cardiac apoptosis and in restoring cardiac brain natriuretic peptide in association with reduced cardiac ACE and AT1 receptor gene expression. In contrast to the ramipril treatment, the favorable effect of E2 on cardiac apoptosis occurred independently from changes in SBP. No synergistic effect was observed when the two treatments were combined.
CONCLUSION: These data show that ovariectomy stimulates myocardium apoptosis by a mechanism involving Bax and Bcl-2 genes. The antiapoptotic effect of E2 and ACE inhibitor treatment was linked to a downregulation of cardiac RAS.
Authors:
Bruno Fabris; Riccardo Candido; Monica Bortoletto; Barbara Toffoli; Stella Bernardi; Marco Stebel; Moreno Bardelli; Lorena Zentilin; Mauro Giacca; Renzo Carretta
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  29     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  273-81     Citation Subset:  IM    
Affiliation:
Dipartimento Universitario Clinico di Scienze Mediche Tecnologiche e Traslazionali, University of Trieste, Trieste, Italy. b.fabris@fmc.units.it
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