Differential participation of angiotensin II type 1 and 2 receptors in the regulation of cardiac cell death triggered by angiotensin II.
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.
Aránguiz-Urroz
Pablo
P
Centro FONDAP Estudios Moleculares de la Célula, Facultad Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
Soto
Dagoberto
D
Contreras
Ariel
A
Troncoso
Rodrigo
R
Chiong
Mario
M
Montenegro
José
J
Venegas
Daniel
D
Smolic
Christian
C
Ayala
Pedro
P
Thomas
Walter G
WG
Lavandero
Sergio
S
Díaz-Araya
Guillermo
G
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D014161:Transduction, Genetic
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D002118:Calcium