[Effect of angiotensin II and aldosterone on the proliferation of cardiac fibroblasts in rats].
OBJECTIVE
To investigate the effect of angiotensin II (ang II), aldosterone (ald) and their receptor antagonists losartan (los) and spironolactone (spi) on the proliferation and collagen production of cardiac fibroblasts (CFs) in rats.


METHODS
CFs were isolated from neonatal SD rats by collagenase II method and purified with differential attachment and detachment method. The 3 or 4 passages of the CFs were divided into the following groups: angiotensin II, angiotensin II+aldosterone, aldosterone, angiotensin II+losartan, and aldosterone+spironolactone. The cell viability of the CFs was assessed by Cell Counting Kit-8 (CCK-8) after the drug administration. The mRNA and protein expression levels of COL1A1, COL3A1, MMP1 and TIMP1 were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot respectively.


RESULTS
Ang II and Ald facilitated the proliferation rate of the CFs independently compared with that in the control group (38.5% vs 28.5%; P<0.05), and the proliferation rate in the ang II+ald group was higher than that in the ang II group and ald group alone (54.4%, P<0.05). Los and spi inhibited the effect induced by ang II and ald respectively (P<0.05). Compared with the control group, ang II and ald significantly enhanced COL1A1, COL3A1 and MMP1 expression both at the mRNA and protein levels (P<0.05), but the TIMP1 expression was inhibited (P<0.05), which could be abolished by corresponding receptor antagonists los and spi (P<0.05).


CONCLUSIONS
Ang II and ald can promote the proliferation of CFs, and the COL1A1 and COL3A1 expression is enhanced both at mRNA and protein levels. Ang II and ald have synergistic effect when they are used together, while los and spi may restrain the effect. The mechanism is probably linked with the balance of MMPs/TIMPs.
Department of Cardiology, General Hospital of the PLA, Beijing 100853.
Yongjin
Y
Xie
Meisheng
M
Yan
Luyue
L
Gai
D000450:Aldosterone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000494:pharmacology
D012333:RNA, Messenger; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D003094:Collagen; D019808:Losartan