Resveratrol and polydatin as modulators of Ca²⁺ mobilization in the cardiovascular system

In the cardiovascular system, Ca²⁺ controls cardiac excitation-contraction coupling and vascular contraction and dilation. Disturbances in intracellular Ca²⁺ homeostasis induce malfunctions of the cardiovascular system, including cardiac pump dysfunction, arrhythmia, remodeling, and apoptosis, as well as hypertension and impairment of vascular reactivity. Therefore, developing drugs and strategies manipulating Ca²⁺ handling are highly valued in the treatment of cardiovascular disease. Resveratrol (Res) and polydatin (PD), a Res glucoside, have been well established to have beneficial effects on improving cardiovascular function. Studies from our laboratory and others have demonstrated that they exhibit inotropic effects on normal heart and therapeutic effects on hypertension, cardiac ischemia/reperfusion injury, hypertrophy, and heart failure by manipulating Ca²⁺ mobilization. The actions of Res and PD on Ca²⁺ signals delicately manipulated by multiple Ca²⁺ -handling proteins are pleiotropic and somewhat controversial, depending on cellular species and intracellular oxidative status. Here, we focus on the effects of Res and PD on controlling Ca²⁺ homeostasis in the heart and vasculature under normal and diseased conditions and highlight the key direct and indirect molecules mediating these effects.