title: Resveratrol attenuates the Na(+)-dependent intracellular Ca(2+) overload by inhibiting H(2)O(2)-induced increase in late sodium current in ventricular myocytes.
abstract: OBJECTIVE
  Resveratrol has been demonstrated to be protective in the cardiovascular system. The aim of this study was to assess the effects of resveratrol on hydrogen peroxide (H(2)O(2))-induced increase in late sodium current (I(Na.L)) which augmented the reverse Na(+)-Ca(2+) exchanger current (I(NCX)), and the diastolic intracellular Ca(2+) concentration in ventricular myocytes.
  
  
  METHODS
  I(Na.L), I(NCX,) L-type Ca(2+) current (I(Ca.L)) and intracellular Ca(2+) properties were determined using whole-cell patch-clamp techniques and dual-excitation fluorescence photomultiplier system (IonOptix), respectively, in rabbit ventricular myocytes.
  
  
  RESULTS
  Resveratrol (10, 20, 40 and 80 µM) decreased I(Na.L) in myocytes both in the absence and presence of H(2)O(2) (300 µM) in a concentration dependent manner. Ranolazine (3-9 µM) and tetrodotoxin (TTX, 4 µM), I(Na.L) inhibitors, decreased I(Na.L) in cardiomyocytes in the presence of 300 µM H(2)O(2). H(2)O(2) (300 µM) increased the reverse I(NCX) and this increase was significantly attenuated by either 20 µM resveratrol or 4 µM ranolazine or 4 µM TTX. In addition, 10 µM resveratrol and 2 µM TTX significantly depressed the increase by 150 µM H(2)O(2) of the diastolic intracellular Ca(2+) fura-2 fluorescence intensity (FFI), fura-fluorescence intensity change (△FFI), maximal velocity of intracellular Ca(2+) transient rise and decay. As expected, 2 µM TTX had no effect on I(Ca.L).
  
  
  CONCLUSIONS
  Resveratrol protects the cardiomyocytes by inhibiting the H(2)O(2)-induced augmentation of I(Na.L.)and may contribute to the reduction of ischemia-induced lethal arrhythmias.
authors.affiliation: Cardio-Electrophysiological Research Laboratory, Medical College, Wuhan University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Qian
authors.forename: Jihua
authors.initials: J
authors.lastname: Ma
authors.forename: Peihua
authors.initials: P
authors.lastname: Zhang
authors.forename: Antao
authors.initials: A
authors.lastname: Luo
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ren
authors.forename: Linghao
authors.initials: L
authors.lastname: Kong
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology / Q000379:methods; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007511:Ischemia; D008297:Male; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D011817:Rabbits; D000069458:Ranolazine; D000077185:Resveratrol; D012964:Sodium / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013696:Temperature; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000083:Acetanilides; D000975:Antioxidants; D010879:Piperazines; D013267:Stilbenes; D013779:Tetrodotoxin; D012964:Sodium; D000069458:Ranolazine; D006861:Hydrogen Peroxide; D000077185:Resveratrol; D002118:Calcium