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ȣ - 510704 147 |
| Anti-atrial fibrillation effects of losartan by suppression of TNF alpha activation in HF |
| 고신의대 복음병원 순환기내과 |
| 허정호, 차태준, 구상호, 최연주, 최인수, 유찬희, 이재우 |
Background: Atrial fibrillation (AF) is the most common sustained arrhythmia. Inflammation is a well-known cause of AF. Tumor necrosis factor-α (TNFα), is an inflammatory cytokine that has been implicated in the pathogenesis of cardiovascular diseases. Here, we investigated AF promoting effect of TNFα and anti-arrhythmic effects of losartan by suppression of angiotensin II induced TNFα activation. Methods: A rat myocardial infarction (MI) model was used. Two days after induction of MI, rats were randomized into 3 groups: the sham group, the MI group, and the MI+Losar group (losartan 10mg/kg/day for 10 weeks). Echocardiography, AF induction, and atrial fibrous tissue content analysis were done. Western blotting of TNFα, angiotensin I/II, induced nitric oxide synthase (iNOS) were done. Results: Ejection fractions were significantly decreased in MI group. Fibrosis quantification showed significantly increased left atrial fibrosis in MI and significantly attenuated in MI+Losar group. Duration of AF were increased in MI group and significantly decreased in MI+Losar group. Left atrial tissue western blotting showed TNFα, Angiotensin I/II, and iNOS were significantly increased in MI group, these were significantly decreased in MI+Losar group. Conclusion: HF left atrial tissue showed increased TNFα protein expression. It was induced by increased tissue angiotensin II concentration. Losartan prevents these changes. This in novel anti-arrhythmic effects of losartan.
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Plus Web Editor Control By Ensys co., Ltd
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Sham |
MI |
MI+Losar |
|
EF(%) |
90.7±1.34
(n=10) |
37.2±3.77*
(n=10) |
47.1±6.11
(n=10) |
|
Fibrosis(%) |
0.25±0.03
(n=7) |
2.22±0.25*
(n=7) |
0.90±0.12#
(n=7) |
|
AF
duration(sec) |
0.4±0.4
(n=10) |
906±297.9*
(n=10) |
180±180.0#
(n=10) |
|
eNOS |
12.84±1.13
(n=6) |
6.56±1.66*
(n=6) |
11.65±1.39
(n=6) |
|
iNOS |
0.25±0.11
(n=9) |
6.09±1.55*
(n=10) |
2.51±0.44
(n=10) |
|
TNF alpha |
0.54±0.04
(n=6) |
1.12±0.06*
(n=6) |
0.69±0.05#
(n=6) |
|
Angiotensin
I/II |
0.32±0.02
(n=6) |
0.56±0.03*
(n=6) |
0.41±0.03#
(n=6) |
Mean±SE,
*p<0.05
sham versus MI, #p<0.05 MI
versus MI+Losar
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