In vitro electrophysiological mechanisms for antiarrhythmic efficacy of resveratrol, a red wine antioxidant.
Resveratrol (trans-3, 4', 5-trihydroxystilbene), a natural antioxidant derived from grapes, has beneficial effects against coronary heart disease. Its electrophysiological characteristics for antiarrhythmic efficacy are largely unknown; thus, this study aims to explore the resveratrol's antiarrhythmic effects and conduction system in isolated hearts as well as its electrophysiological effects on cardiac myocytes. In the experiment, resveratrol suppressed the ischemia/reperfusion-induced ventricular arrhythmias in Langendorff-perfused rat hearts. In the current clamp study of the experiment, resveratrol prolonged the action potential duration (APD(50) and APD(90)) and suppressed the upstroke velocity of the action potential (V(max)). In the voltage clamp study, resveratrol inhibited sodium inward current (I(Na)) in a concentration-dependent manner and negative-shifted the voltage-dependent inactivation curve. Resveratrol also reduced the calcium inward current (I(Ca), 51.2+/-13.3% at 100 microM). Furthermore, the transient (I(to)) and sustained (I(ss)) outward potassium currents were decreased 60.2+/-5.7% and 42.3+/-5.2% after exposure to resveratrol (100 microM), respectively. The inward rectifier potassium current (I(K1)) was also reduced 24.2+/-7.0% in the presence of resveratrol (100 microM). In the isolated heart perfusion model, resveratrol (100 microM) prolonged AV nodal refractory period, the Wenckebach cycle length and the conduction through AV node and His-Purkinje system. In conclusion, resveratrol increased the cardiac effective refractory period mainly through inhibiting the ionic channels including I(Na), I(to) and I(ss) which could contribute to the conversion of ischemia/reperfusion-induced lethal arrhythmias.
Chen
Wen-Pin
WP
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Su
Ming-Jai
MJ
Hung
Li-Man
LM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000150:complications; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology*; D016896:Treatment Outcome; D014920:Wine
D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D015222:Sodium Channels; D013267:Stilbenes; D000077185:Resveratrol; D002118:Calcium