[An experimental study of expression of angiotension converting enzyme 2 in myocardium and effect of telmisartan treatment in pressure-overloaded rats].
OBJECTIVE
To study the effect of hypertension and telmisartan treatment on the protein and gene expression of cardiac angiotensin-converting enzyme 2 (ACE2) in pressure-overloaded rats.


METHODS
Coarctation of suprarenal abdominal aorta was reproduced in 8 week-old male Sprague-Dawley (SD) rats and then randomized into 4 groups, including a sham group (n=15), a suprarenal aortic coarctation group (model group, n=12), a suprarenal aortic coarctation with low-dose Telmisartan treatment group (low-dose group, 2 mgxkg(-1)xd(-1), n=11) and a suprarenal aortic coarctation with high-dose Telmisartan treatment group(high-dose group, 10 mgxkg(-1)xd(-1), n=13). Telmisartan or equivalent amount of normal saline was gavaged 24 hours before the operation and once every day afterwards for 3 weeks. At the end of 3 weeks, the concentrations of angiotensin (AngII) in plasma and myocardium were measured by radioimmunoassay. Changes in both protein quantity and gene expressions of both ACE2 and ACE were determined by Western blotting analysis and reverse transcription-polymerase chain reaction (RT-PCR) technique, respectively.


RESULTS
Suprarenal abdominal aortic coarctation induced a significant increase in the plasma and myocardium AngII concentration [plasma: (495.1+/-55.6) ng/L vs. (269.2+/-39.5)ng/L, myocardium: (103.6+/-23.7) ng/g vs. (49.5+/-13.5) ng/g, both P<0.01] and expressions of gene and protein of ACE (P<0.01) and ACE2 (P<0.05). Telmisartan further increased the concentration of AngII in plasma and myocardium in a dose-dependent manner [plasma: (702.2+/-40.6) ng/L vs. (612.6+/-35.5) ng/L, myocardium (211.5+/-21.5) ng/g vs. (189.6+/-43.6) ng/g, both P<0.05], and induced a dose-dependent increase in both protein and gene expression of ACE2 (protein 1.16+/-0.06 vs. 0.79+/-0.04, gene 0.54+/-0.08 vs. 0.41+/-0.04, both P<0.05). Expression of ACE2 protein in low-dose and high-dose groups was increased by 1.0 and 1.58 folds respectively, and gene was increased by 1.3 and 1.6 folds (all P<0.05). The expression of ACE protein and gene in model group increased significantly (protein: 2.10+/-1.07 vs. 1.02+/-0.05, gene: 1.93+/-0.09 vs. 0.26+/-0.09, both P<0.01). Telmisartan had no significant effect on ACE gene and protein expressions (both P>0.05).


CONCLUSIONS
Suprarenal abdominal aortic coarctation induced a significant increases of ACE and ACE2 gene and protein expressions. Telmisartan induces a dose-dependent increases of cardiac ACE2 gene and protein expression,which may be the mechanism of its therapeutic effects.
Wang
Li-jun
LJ
Department of Cardiology, The Affiliated Baoan Hospital of Nanfang Medical University, Shenzhen 518101, Guangdong, China. wang.j63@163.com
Ma
Hong
H
Liao
Xin-xue
XX
He
Jian-gui
JG
Zhang
Wen-wu
WW
Tian
Fang
F
Cai
Yi-ming
YM
Gu
Hai-bo
HB
Hao
Yan-hua
YH
Hu
Xue-song
XS
Zou
Hong-mei
HM
Zhou
Qiu-ling
QL
D000804:Angiotensin II / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001017:Aortic Coarctation / Q000188:drug therapy / Q000378:metabolism*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan
D001562:Benzimidazoles; D001565:Benzoates; D012333:RNA, Messenger; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D000077333:Telmisartan