Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2＋ overload

• Published in: Acta pharmacologica Sinica 2013-09, Vol.34 (9), p.1164-1173
• Main Authors: Li, Wei, Wang, Yue-peng, Gao, Ling, Zhang, Peng-pai, Zhou, Qing, Xu, Quan-fu, Zhou, Zhi-wen, Guo, Kai, Chen, Ren-hua, Yang, Huang-tian, Li, Yi-gang
• Format: Article
• Language: English
• Subjects: Animals; Arrhythmias, Cardiac - metabolism; Arrhythmias, Cardiac - prevention & control; Biomedical and Life Sciences; Biomedicine; Calcium - metabolism; Cells, Cultured; Heart Ventricles - cytology; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Immunology; Internal Medicine; Male; Medical Microbiology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Original; original-article; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pharmacology/Toxicology; Rabbits; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; Stilbenes - pharmacology; Stilbenes - therapeutic use; Vaccine; Western印迹; 保护; 心室肌细胞; 心律失常; 氧化应激; 白藜芦醇; 诱导; 超载
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2013.82

Aim： To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca2＋ overload in ventricular myocytes and to explore the underlying mechanisms. Methods： Hydrogen peroxide （H2O2, 200 μmol/L）） was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca2＋ （[Ca2＋]i）. Ca2＋/calmodulin-dependent protein kinases II （CaMKII） activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na＋ and Ca2＋ currents were examined using whole-cell recording in myocytes. Results： H2O2 markedly prolonged Ca2＋ transient duration （CaTD）, and induced early afterdepolarization （EAD）-like and delayed afterdepolarization （DAD）-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol （30 or 50 μmol/L） dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol （50 μmol/L） effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca2＋]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na＋ current （INa,L） and L-type Ca2＋ current （ICa,L） in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol. Conclusion： Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2＋ overload through inhibition of INa,L/ICa,L, reduction of ROS generation, and prevention of CaMKII activation.