| Objective: Resveratrol (trans-3, 4', 5-trihydroxystilbene) is a common phytoalexin that is found in a few edible materials, such as grape skins, peanuts, and red wine. It has been reported to have a variety of estrogenic, anti-inflammatory, anti-platelet, and anti-carcinogenic effects. Accumulating evidences supported that resveratrol might serve as a cardioprotective agent. Resveratrol could protect the heart from ischemia-reperfusion injury. It decreased plasma triglycerides and cholesterol accumulation in the aorta and prevented atherosclerosis. Moreover, it relaxed the coronary arteries. It was reported that resveratrol pretreatment both reduced the incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) after ischemia-reperfusion. It has been well recognized that triggered activity (TA) caused by delayed afterdepolarization (DAD) could be an important mechanism underlying some cardiac arrhythmias like those due to digitalis or occurring after myocardial infarction and DAD in cardiac cells has been attributed to Ca2+ overload. Recently, we found that resveratrol decreased the amplitude of action potential (APA) and maximal velocity of phase 0 depolarization (Vmax) in partially depolarized papillary muscles. These effects were likely due to a decrease of calcium influx. Therefore, we postulate that resveratrol may exert inhibitory effects on DAD and TA. The purpose of this study was to investigate the effects of resveratrol on delayed afterdepolarization (DAD) and triggered activity (TA) induced by ouabain in guinea pig papillary muscles and the underlying mechanism. Methods: Male guinea pig was killed by a heavy blow on the head and the heart was quickly removed and placed in cold (04℃) oxygenated (95% O2 and 5% CO2) K-H solution. The papillary muscle was excised from right ventricle and fixed on a thin silicon disc and perfused (4 ml/min) with K-H solution at 35.5 ±0.5℃. The preparation was paced by square pulse (1.67 Hz, 1 ms, 1.5 times threshold) generated by an electronic stimulator. The transmembrane action potentials were recorded using intracellular microelectrode technique. Drugs were administered and the electrophysiological effects were observed. Results: (1) DAD and TA induced by ouabain (1 μmol/L) were inhibited by pretreatment with resveratrol (30, 60, and 120 μmol/L) in a concentration-dependent manner. Resveratrol (30, 60, and 120 μmol/L) decreased the amplitude of DAD (from 11.1 ±0.9 mV to 9.7 ±1.2 mV, 5.8 ±0.8 mV and 3.4 ±0.4 mV, respectively) and duration of DAD (from 196.0 ±10.6 ms to 184.3 ±12.5 ms, 146.7 ±8.4 ms and 119.5 ±6.1 ms, respectively), and prolonged the latent period of DAD (from 196.0 ±10.6 min to 184.3 ±12.5 min, 146.7 ±8.4 min and119.5 ±6.1 min, respectively). At the same time, the occurrence of TA was also inhibited (from 71 % to 54 %, 14 % and 0 %, respectively). (2) Pretreatment with L-type calcium channel agonist Bay K8644 could completely abolish the inhitory effects of resveratrol (60 μmol/L); (3) Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a nitric oxide (NO) synthase inhibitor, failed to abolish the above effect of resveratrol (60 μmol/L); (4) 5 μmol/L 17β-estradiol (E2) or 30 μmol/L resveratrol had no effects on DAD and TA, however, resveratrol combined with E2 at the same doses exerted significant inhibitory effects on DAD and TA; (5) Pretreatment with tamoxifen (TAM, 10 μmol/L), an inhibitor of estrogen receptor, also did not blocked the effects of resveratrol (60 μmol/L) on DAD and TA induced by ouabain. Conclusion: All these results indicated that resveratrol exerted an inhibitory effects on DAD and TA induced by ouabain, possibly by reducing calcium influx, which might not be mediated by NO and estrogen receptor. The antiarrhythmic effects of resveratrol may contribute to its cardioprotective action.Objective: Resveratrol (trans-3, 4', 5-trihydroxystilbene) is a common phytoalexin. It has been reported to have a variety of biochemical and physiological actions, including... |
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