| Objective: Resveratrol (trans-3, 4', 5-trihydroxystilbene) is a phenolic phytoalexin present in grape skins and wines, especially red wines. Resveratrol exerts a wide variety of biological effects, including estrogenic, anti-flammatory, antioxidant and anticancer activities. Moreover, accumulating evidence indicates that resveratrol may confer protective action on the cardiovascular system. The cardiovascular benefits of resveratrol may relate to protecting the heart cells from ischemia-reperfusion injury, inhibiting platelet aggregation, and decreasing plasma triglycerides and cholesterol accumulation in the aorta. Furthermore, it can also relax the coronary arteries. Thus, resveratrol may have a potential clinical value in treatment of cardiovascular diseases. In our previous studies, we found that resveratrol shortened the duration of action potential in papillary muscles in normal guinea pig and also decreased the maximal velocity of phase 0 depolarization in partially depolarized papillary muscles. These effects were likely due to a decrease of calcium influx. Little is known, however, about the effects of resveratrol on electrophysiology of cardiomycytes and underlying mechanisms. In the present study, we observed the electrophysiological effects of resveratrol on cardiomycytes and investigated the mechanism(s) involved by using intracellular microelectrode technique and laser scanning confocal microscopy. Methods: Rabbit (♂) was killed with a single blow on head and the heart was removed and placed in cold (04℃) oxygenated (95% O2 and 5% CO2) Krebs-Henseleit (K-H) solution. The preparation of SAN was isolated carefully and pinned down on a thin silicon disc, perfused with K-H solution (4 ml/min) at 36.0 ±0.5℃. The action potential was recorded using intracellular microelectrode technique. Drugs were administered and the changes of AP were observed. Results: (1) Resveratrol (30120 μmol/L) not only significantly decreased the amplitude of action potential (APA) [from (69±7) mV to (63±6) mV (P<0.01)] and maximal rate of depolarization (Vmax) [from (8.1±0.8) V/s to (6.2±1.1) V/s (P<0.01)], but also decreased the velocity of diastolic (phase 4) depolarization (VDD) [from (61±7) mV/s to (34±11) mV/s (P<0.01)] and rate of pacemaker firing (RPF) [from (168±16) beat/min to (109±13) beat/min (P<0.01)]. While the maximal diastolic potential (MDP) and the duration of 90% repolarization of action potential (APD90) were not affected. (2) Pretreatment with L-type calcium channel agonist Bay K8644 (0.5 μmol/L) could completely antagonize the effects of resveratrol (60 μmol/L). (3) Simultaneously applying cesium chloride (CsCl, 2 mmol/L), a hyperpolarization-activated current (If) blocker, and tetraethylammonium chloride (TEA, 20mmol/L), a potassium channel antagonist, could not abolish the effects of resveratrol on SA node cells. (4) Pretreatment with 0.5 mmol/L L-NAME, a NO synthase inhibitor, failed to block the electrophysiological effects of resveratrol. Conclusion: All these results suggest that the effects of resveratrol on pacemaker cells in SA node of rabbits are likely due to the reduction in calcium influx via a NO-independent manner. Objective: Resveratrol (trans-3, 4', 5-trihydroxystilbene) is a phenolic phytoalexin present in grape skins and wines, especially red wines. Accumulating evidence indicates that resveratrol may confer protective action on the cardiovascular system. The cardiovascular benefits of resveratrol may relate to protecting the heart cells from ischemia-reperfusion injury, inhibiting platelet aggregation, and decreasing plasma triglycerides and cholesterol accumulation in the aorta. Furthermore, it can also relax the coronary arteries. In ourprevious studies, we found that resveratrol shortened the duration of action potential in papillary muscles in normal guinea pig and also decreased the maximal velocity of phase 0 depolarization in partially depolarized papillary muscles. In addition, resveratrol concentration-dependently inhibited delayed afterdepolarization and tri... |
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