Abstract | INTRODUCTION: METHODS: In acute experiments, dogs were randomly assigned to Sham, Paced and Paced+aliskiren (10 mg kg-1) (Paced+ALS) groups, with 7 dogs in each group. Rapid atrial pacing (RAP) was maintained at 600 bpm for 2 h for paced and Paced+ALS groups and atrial effective refractory periods (AERPs), inducibility of AF (AFi) and average duration time (ADT) were measured. In chronic experiments, there were 5 groups: Sham, Sham+ALS, Paced, Paced+ALS and Paced+ALS+PI3K antagonist wortmannin (WM) (70 μg kg-1 day-1). RAP at 500 beats/min was maintained for 2 weeks. Inflammation and oxidative stress indicators were measured by ELISA assay, echocardiogram and pathology were used to assess atrial structural remodeling, phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/Akt) signaling pathways were studied by RT-PCR and western blotting to evaluate whether the cardioprotective effect of ALS works through PI3K/Akt signaling pathway. RESULTS: The electrophysiological changes were observed after 2-h pacing. The AERP shortened with increased AFi and ADT, which was attenuated by ALS (P < 0.05). After pacing for 2 weeks, oxidative stress and inflammation markers in the Paced group were significantly higher than those in the Sham group (P < 0.01) and were reduced by ALS treatment (P < 0.01). The reduced level of antioxidant enzymes caused by RAP was also found to be elevated in ALS-treated group (P < 0.01). The results of pathology and echocardiography showed that RAP can cause atrial enlargement, fibrosis (P < 0.01), and were attenuated in ALS treatment group. The PI3K/Akt signaling pathway were downregulated induced by RAP. ALS could upregulate the PI3K/Akt pathway expression (P < 0.05). Furthermore, the cardioprotective effects in structural remodeling of ALS were suppressed by WM. CONCLUSIONS: ALS may offer cardioprotection in RAP-induced atrial remodeling, which may partly be ascribed to its anti-inflammatory and anti-oxidative stress action and the regulation of PI3K/Akt signaling pathway.
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Authors | Zhiqiang Zhao, Ruiling Li, Xinghua Wang, Jian Li, Meng Yuan, Enzhao Liu, Tong Liu, Guangping Li |
Journal | Cardiovascular drugs and therapy
(Cardiovasc Drugs Ther)
Vol. 35
Issue 3
Pg. 587-598
(06 2021)
ISSN: 1573-7241 [Electronic] United States |
PMID | 32462265
(Publication Type: Journal Article)
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Chemical References |
- Amides
- Fumarates
- Inflammation Mediators
- aliskiren
- Wortmannin
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Topics |
- Amides
(pharmacology)
- Animals
- Atrial Remodeling
(drug effects)
- Dogs
- Echocardiography
- Female
- Fumarates
(pharmacology)
- Inflammation Mediators
(metabolism)
- Male
- Oxidative Stress
(drug effects)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Random Allocation
- Signal Transduction
(drug effects)
- Wortmannin
(pharmacology)
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