Liu Zheng, Zhang Li-Ping, Ma Hui-Jie, Wang Chuan, Li Ming, Wang Qing-Shan
Department of Physiology, Institute of Basic Medical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
Sheng Li Xue Bao. 2005 Oct 25;57(5):599-604.
Resveratrol (trans-3, 4', 5-trihydroxy stilbene), a phytoalexin found in grape skins and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that resveratrol may have cardioprotective activity. The objective of our study was to investigate the effects of resveratrol on intracellular calcium concentration (Ca(2+)) in rat ventricular myocytes. Ca(2+) was detected by laser scanning confocal microscopy. The results showed that resveratrol (15~60 mumol/L) reduced Ca(2+) in normal and Ca(2+)-free Tyrode's solution in a concentration-dependent manner. The effects of resveratrol on Ca(2+) in normal Tyrode's solution was partially inhibited by pretreatment with sodium orthovanadate (Na3VO4, 1.0 mmol/L, P<0.01), an inhibitor of protein tyrosine phosphatase, or L-type Ca(2+) channel agonist Bay K8644 (10 mumol/L, P<0.05), but could not be antagonized by NO synthase inhibitor L-NAME (1.0 mmol/L). Resveratrol also markedly inhibited the ryanodine-induced Ca(2+) increase in Ca(2+)-free Tyrode's solution (P<0.01). When Ca(2+) waves were produced by increasing extracellular Ca(2+) concentration from 1 to 10 mmol/L, resveratrol (60 mumol/L) could reduce the velocity and duration of propagating waves, and block the propagating waves of elevated Ca(2+). These results suggest that resveratrol may reduce the Ca(2+) in isolated rat ventricular myocytes. The inhibition of voltage-dependent Ca(2+) channel and tyrosine kinase, and alleviation of Ca(2+) release from sarcoplasmic reticulum (SR) are possibly involved in the effects of resveratrol on rat ventricular myocytes. These findings could help explain the protective activity of resveratrol against cardiovascular disease.
白藜芦醇(反式-3,4',5-三羟基芪)是一种在葡萄皮和红酒中发现的植物抗毒素,据报道具有广泛的生物学和药理学特性。据推测,白藜芦醇可能具有心脏保护活性。我们研究的目的是探讨白藜芦醇对大鼠心室肌细胞内钙浓度(Ca(2+))的影响。通过激光扫描共聚焦显微镜检测Ca(2+)。结果表明,白藜芦醇(15~60 μmol/L)在正常和无钙的台氏液中均以浓度依赖性方式降低Ca(2+)。在正常台氏液中,白藜芦醇对Ca(2+)的作用部分被蛋白酪氨酸磷酸酶抑制剂原钒酸钠(Na3VO4,1.0 mmol/L,P<0.01)或L型钙通道激动剂Bay K8644(10 μmol/L,P<0.05)预处理所抑制,但不能被一氧化氮合酶抑制剂L-NAME(1.0 mmol/L)拮抗。白藜芦醇还显著抑制了无钙台氏液中ryanodine诱导的Ca(2+)升高(P<0.01)。当通过将细胞外钙浓度从1 mmol/L增加到10 mmol/L产生钙波时,白藜芦醇(60 μmol/L)可降低传播波的速度和持续时间,并阻断升高的Ca(2+)传播波。这些结果表明,白藜芦醇可能降低离体大鼠心室肌细胞中的Ca(2+)。对电压依赖性钙通道和酪氨酸激酶的抑制以及肌浆网(SR)钙释放的减轻可能参与了白藜芦醇对大鼠心室肌细胞的作用。这些发现有助于解释白藜芦醇对心血管疾病的保护活性。