Role of angiotensin II type 2 receptor during regression of cardiac hypertrophy in spontaneously hypertensive rats

Shant Der Sarkissian, Bun Seng Tea, Rhian M. Touyz, Denis Deblois, Taben Hale

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We previously reported that the AT1 receptor antagonist valsartan and the angiotensin converting enzyme (ACE) inhibitor enalapril decrease DNA synthesis and stimulate apoptosis in interstitial fibroblasts and epicardial mesothelial cells during regression of ventricular hypertrophy in spontaneously hypertensive rats (SHR). To examine the role of the AT2 receptor in this model, we studied hearts from SHR treated with valsartan or enalapril either alone or combined with the AT2 antagonist PD123319 for 1 or 2 weeks. Apoptosis was evaluated by quantification of DNA fragmentation or by TUNEL labeling. At 1 week, valsartan significantly increased ventricular DNA fragmentation, increased apoptosis in epicardial mesothelial cells, and decreased DNA synthesis. At 2 weeks, ventricular DNA content and cardiomyocyte cross-sectional area were significantly reduced. These valsartan-induced changes were attenuated by PD123319 co-administration. However, valsartan-induced increases in apoptosis of left ventricular interstitial non-cardiomyocytes was unaffected by the AT2 blocker. Enalapril-induced changes were similar to those observed with valsartan but were not affected by co-treatment with PD123319. These results demonstrate that AT1 and AT2 receptors act in a coordinated yet cell-specific manner to regulate cell growth and apoptosis in the left ventricle of SHR during AT1 receptor blockade but not ACE inhibition.

Original languageEnglish (US)
Pages (from-to)118-127
Number of pages10
JournalJournal of the American Society of Hypertension
Volume7
Issue number2
DOIs
StatePublished - Mar 2013

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Valsartan
Angiotensin Type 2 Receptor
Cardiomegaly
Inbred SHR Rats
Enalapril
Apoptosis
DNA Fragmentation
DNA
In Situ Nick-End Labeling
Peptidyl-Dipeptidase A
Angiotensin-Converting Enzyme Inhibitors
Cardiac Myocytes
Hypertrophy
Heart Ventricles
Fibroblasts

Keywords

  • ACE inhibitor
  • apoptosis
  • AT antagonist
  • fibroblast

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Internal Medicine

Cite this

Role of angiotensin II type 2 receptor during regression of cardiac hypertrophy in spontaneously hypertensive rats. / Der Sarkissian, Shant; Tea, Bun Seng; Touyz, Rhian M.; Deblois, Denis; Hale, Taben.

In: Journal of the American Society of Hypertension, Vol. 7, No. 2, 03.2013, p. 118-127.

Research output: Contribution to journalArticle

Der Sarkissian, Shant ; Tea, Bun Seng ; Touyz, Rhian M. ; Deblois, Denis ; Hale, Taben. / Role of angiotensin II type 2 receptor during regression of cardiac hypertrophy in spontaneously hypertensive rats. In: Journal of the American Society of Hypertension. 2013 ; Vol. 7, No. 2. pp. 118-127.
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