Differential participation of angiotensin II type 1 and 2 receptors in the regulation of cardiac cell death triggered by angiotensin II

Am J Hypertens. 2009 May;22(5):569-76. doi: 10.1038/ajh.2009.32. Epub 2009 Mar 19.

Abstract

Background: The Angiotensin II (Ang II) type 1 (AT(1)R) and type 2 (AT(2)R) receptors are increased in the heart following myocardial infarction and dilated cardiomyopathy, yet their contribution at a cellular level to compensation and/or failure remains controversial.

Methods: We ectopically expressed AT(1)R and AT(2)R in cultured adult rat cardiomyocytes and cardiac fibroblasts to investigate Ang II-mediated cardiomyocyte hypertrophy and cardiac cell viability.

Results: In adult rat cardiomyocytes, Ang II did not induce hypertrophy via the AT(1)R, and no effect of Ang II on cell viability was observed following AT(1)R or AT(2)R expression. In adult rat cardiac fibroblasts, Ang II stimulated cell death by apoptosis via the AT(1)R (but not the AT(2)R), which required the presence of extracellular calcium, and induced a rapid dissipation of mitochondrial membrane potential, which was significant from 8 h.

Conclusions: We conclude that Ang II/AT(1)R triggers apoptosis in adult rat cardiac fibroblasts, which is dependent on Ca2+ influx.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Sarcosine-8-Isoleucine Angiotensin II / metabolism
  • Adenoviridae / genetics
  • Angiotensin II / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Calcium / physiology
  • Cell Death / drug effects
  • Cells, Cultured
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / physiology*
  • Receptor, Angiotensin, Type 2 / physiology*
  • Transduction, Genetic

Substances

  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Angiotensin II
  • 1-Sarcosine-8-Isoleucine Angiotensin II
  • Calcium