Departamento de Farmacología y Terapéutica, Facultad de Medicina, Instituto Teófilo Hernando, Universidad Autónoma de Madrid (ITH/UAM), Madrid, Spain; Department of Molecular Pathobiology, New York University College of Dentistry (NYU), New York, USA.
Departamento de Farmacologia, Escola Paulista de Medicina da Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Cell Signal. 2020 Dec;76:109811. doi: 10.1016/j.cellsig.2020.109811. Epub 2020 Oct 17.
Resveratrol (RESV) is one of the most abundant polyphenol-stilbene compounds found in red wine with well-established cardioprotective and antihypertensive effects. Hyperactivity of the sympathoadrenal axis seems to be one of the major contributing factors in the pathogenesis of human essential hypertension. Alterations in outward voltage-dependent potassium currents (I) and inward voltage-dependent sodium (I), calcium (I) and nicotinic (I) currents, CCs excitability, Ca homeostasis, and catecholamine exocytosis were previously related to the hypertensive state. This raised the issue of whether in vivo long-term RESV treatment can directly act as a modulator of Ca influx or a regulator of ion channel permeability in CCs. We monitored outward and inward currents, and cytosolic Ca concentrations ([Ca]) using different pharmacological approaches in CCs from normotensive (WKY) and hypertensive (SHR) animals chronically exposed to trans-RESV (50 mg/L/v.o, 28 days). The long-term RESV treatment prevented the increase of the systolic blood pressure (SBP) in SHR, without reversion of cardiac hypertrophy. We also found an increase of the outward I, reduction in inward II, and I, and the mitigation of [Ca] overload in CCs from SHR at the end of RESV treatment. Our data revealed that electrophysiological alterations of the CCs and in its Ca homeostasis are potential new targets related to the antihypertensive effects of long-term RESV treatment.
白藜芦醇(RESV)是红酒中含量最丰富的多酚类化合物之一,具有明确的心脏保护和降压作用。交感肾上腺轴的过度活跃似乎是人类原发性高血压发病机制的主要因素之一。外向电压依赖性钾电流(I)和内向电压依赖性钠(I)、钙(I)和烟碱(I)电流、CCs 的兴奋性、钙稳态和儿茶酚胺胞吐的改变与高血压状态有关。这就提出了一个问题,即在体内长期 RESV 治疗是否可以直接作为 Ca 内流的调节剂或 CCs 离子通道通透性的调节剂。我们使用不同的药理学方法在长期暴露于反式 RESV(50mg/L/v.o,28 天)的正常血压(WKY)和高血压(SHR)动物的 CCs 中监测外向和内向电流以及细胞浆 Ca 浓度([Ca])。长期 RESV 治疗可预防 SHR 收缩压(SBP)升高,而不逆转心脏肥大。我们还发现,在 RESV 治疗结束时,SHR 的 CCs 中外向 I 增加,内向 II 和 I 减少,[Ca]过载减轻。我们的数据表明,CCs 的电生理改变及其 Ca 稳态是与长期 RESV 治疗的降压作用相关的潜在新靶点。