@article{APS6805,
author = {Wei Li and Yue-peng Wang and Ling Gao and Peng-pai Zhang and Qing Zhou and Quan-fu Xu and Zhi-wen Zhou and Kai Guo and Ren-hua Chen and Huang-tian Yang and Yi-gang Li},
title = {Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca 2+ overload},
journal = {Acta Pharmacologica Sinica},
volume = {34},
number = {9},
year = {2016},
keywords = {},
abstract = {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.
Keywords: resveratrol; cardiop},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/6805}
}