Ranolazine improves oxidative stress and mitochondrial function in the atrium of acetylcholine-CaCl2 induced atrial fibrillation rats.

Abstract

AIMS:

Ranolazine, an antianginal agent used for chronic stable angina treatment, was demonstrated to be effective in atrial fibrillation (AF) treatment. The aim of this study was to explore the molecular mechanisms of its anti-AF effects.

MAIN METHODS:

AF rat model was established using acetylcholine (ACh)-CaCl2 injection for 7days followed by ACh infusion into the heart. Prior to ACh infusion, ranolazine at 10.7mg/kg/0.5ml was injected into vein and followed by 0.56mg/kg/min infusion. Blood pressure and electrocardiogram were monitored during the infusion. Histological changes of atrial tissue were observed after H&E staining. Activities and protein expression of NADPH oxidase-4, xanthine oxidase, glutathione peroxidase and superoxide dismutase were examined using commercial assay kits and Western botting, respectively. Mitochondrial functions were evaluated through membrane potential, ATP production, activities of complex I and III and reactive oxygen species production. Apoptosis was measured using TUNEL staining. Protein expression of apoptotic proteins Bcl-2, Bax and cleaved-caspase 3 and Akt/mTOR signaling proteins were detected using Western blotting.

KEY FINDINGS:

Results demonstrated that ranolazine attenuated AF in ACh-CaCl2-exposed rats. In addition, ranolazine restored mitochondrial function, suppressed oxidative stress, and inhibited atrial cells apoptosis. Furthermore, the activated Akt/mTOR signaling pathway induced by AF was further activated by ranolazine.

SIGNIFICANCE:

The present study confirms the effects of ranolazine on AF rats induced by ACh-CaCl2, and provides evidence that the anti-AF effects are associated with the restoration of mitochondrial function and activation of the Akt/mTOR signaling pathway in atrial tissue.

• Authors: Deling Zou, Ning Geng, Yanli Chen, Li Ren, Xingli Liu, Jiye Wan, Sicong Guo, Shaojun Wang
• Journal: Life sciences (Life Sci) Vol. 156 Pg. 7-14 (Jul 01 2016) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 27208652 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Ranolazine
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Calcium Chloride
• Acetylcholine

Topics

• Acetylcholine
• Animals
• Apoptosis (drug effects)
• Atrial Fibrillation (pathology)
• Calcium Chloride
• Heart Atria (drug effects, metabolism, pathology)
• Hemodynamics (drug effects)
• Male
• Mitochondria (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Ranolazine (pharmacology)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)