白藜芦醇对哇巴因所致豚鼠乳头状肌迟后去极化及触发活动的效应(英文)

Effects of resveratrol on delayed afterdepolarization and triggered activity induced by ouabain in guinea pig papillary muscles

研究旨在应用标准玻璃微电极技术,观察白藜芦醇对哇巴因所引起的离体豚鼠乳头状肌迟后去极化(delayedafterdepolarization,DAD)及触发活动(triggeredactivity,TA)的效应。结果显示:(1)预先给予白藜芦醇(30、60、120μmol/L)可剂量依赖性地抑制哇巴因所引起的乳头状肌DAD及TA;(2)预先应用L型钙通道开放剂BayK8644(0.25μmol/L),可取消白藜芦醇的上述效应;(3)预先应用一氧化氮合酶抑制剂L-NAME(1mmol/L),对白藜芦醇的上述效应无影响;(4)单独应用17β-雌二醇(E2,5μmol/L)或白藜芦醇(30μmol/L)对DAD及TA无明显影响,而联合应用相同剂量的E2和白藜芦醇则对DAD及TA产生明显的抑制效应;(5)预先应用雌激素受体拮抗剂他莫昔芬(10μmol/L)不能取消白藜芦醇对DAD及TA的抑制作用。以上结果表明,白藜芦醇具有抑制乳头状肌DAD及TA的作用,这一效应可能与其抑制钙离子内流有关,但此作用机制中NO和雌激素受体的作用并不显著。白藜芦醇这种抗心律失常作用对于心血管系统具有一定的保护意义。

The purpose of this study was to investigate the effects of resveratrol on delayed afterdepolarization (DAD) and triggeredactivity (TA) induced by ouabain in guinea pig papillary muscles and the underlying mechanism. Action potentials were recorded usingintracellular microelectrode technique. The results obtained are as follows: (1) DAD and TA induced by ouabain (1 μmol/L) wereinhibited by pretreatment with resveratrol (30, 60, and 120 μmol/L) in a concentration-dependent manner; (2) 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 ofresveratrol (60 μmol/L ); (3 ) 5 μmol/L 17β-estradiol (E2) or 30 μmol/L resveratrol had no effects on DAD and TA, however, resveratrolcombined with E2 at the same doses exerted significant inhibitory effects on DAD and TA; (4) Pretreatment with tamoxifen (TAM, 10μmol/L), an inhibitor of estrogen receptor, also did not blocked the effects of resveratrol (60 μmol/L) on DAD and TA induced byouabain. All these results indicated that resveratrol exerted an inhibitory effects on DAD and TA induced by ouabain, possibly byreducing calcium influx, which might not be mediated by NO and estrogen receptor. The antiarrhythmic effects of resveratrol maycontribute to its cardioprotective action.