Stimulation of cardiac apoptosis in ovariectomized hypertensive rats: Potential role of the renin-angiotensin system

Bruno Fabris; Riccardo Candido; Monica Bortoletto; Barbara Toffoli; Stella Bernardi; Marco Stebel; Moreno Bardelli; Lorena Zentilin; Mauro Giacca; Renzo Carretta

doi:10.1097/HJH.0b013e328340d0d3

Stimulation of cardiac apoptosis in ovariectomized hypertensive rats: Potential role of the renin-angiotensin system

Bruno Fabris^*, Riccardo Candido, Monica Bortoletto, Barbara Toffoli, Stella Bernardi, Marco Stebel, Moreno Bardelli, Lorena Zentilin, Mauro Giacca, Renzo Carretta

^*Corresponding author for this work

Cardiovascular Medicine & Sciences

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	273-281
Number of pages	9
Journal	Journal of Hypertension
Volume	29
Issue number	2
DOIs	https://doi.org/10.1097/HJH.0b013e328340d0d3
Publication status	Published - 1 Feb 2011

Keywords

angiotensin-converting enzyme inhibitors
apoptosis gene expression
estrogens
hypertension
renin-angiotensin system

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1097/HJH.0b013e328340d0d3

Cite this

@article{e4ecf03ca8c849349183e12d8857bf9a,

title = "Stimulation of cardiac apoptosis in ovariectomized hypertensive rats: Potential role of the renin-angiotensin system",

abstract = "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.",

keywords = "angiotensin-converting enzyme inhibitors, apoptosis gene expression, estrogens, hypertension, renin-angiotensin system",

author = "Bruno Fabris and Riccardo Candido and Monica Bortoletto and Barbara Toffoli and Stella Bernardi and Marco Stebel and Moreno Bardelli and Lorena Zentilin and Mauro Giacca and Renzo Carretta",

year = "2011",

month = feb,

day = "1",

doi = "10.1097/HJH.0b013e328340d0d3",

language = "English",

volume = "29",

pages = "273--281",

journal = "Journal of Hypertension",

issn = "0263-6352",

publisher = "Lippincott Williams and Wilkins",

number = "2",

}

TY - JOUR

T1 - Stimulation of cardiac apoptosis in ovariectomized hypertensive rats

T2 - Potential role of the renin-angiotensin system

AU - Fabris, Bruno

AU - Candido, Riccardo

AU - Bortoletto, Monica

AU - Toffoli, Barbara

AU - Bernardi, Stella

AU - Stebel, Marco

AU - Bardelli, Moreno

AU - Zentilin, Lorena

AU - Giacca, Mauro

AU - Carretta, Renzo

PY - 2011/2/1

Y1 - 2011/2/1

N2 - 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.

AB - 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.

KW - angiotensin-converting enzyme inhibitors

KW - apoptosis gene expression

KW - estrogens

KW - hypertension

KW - renin-angiotensin system

UR - http://www.scopus.com/inward/record.url?scp=78651299746&partnerID=8YFLogxK

U2 - 10.1097/HJH.0b013e328340d0d3

DO - 10.1097/HJH.0b013e328340d0d3

M3 - Article

C2 - 21107282

AN - SCOPUS:78651299746

SN - 0263-6352

VL - 29

SP - 273

EP - 281

JO - Journal of Hypertension

JF - Journal of Hypertension

IS - 2

ER -

Stimulation of cardiac apoptosis in ovariectomized hypertensive rats: Potential role of the renin-angiotensin system

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this