Resveratrol Stimulates the Na⁺-Ca²⁺Exchanger on the Plasma Membrane to Reduce Cytosolic Ca²⁺in Rat Aortic Smooth Muscle Cells

Abstract:Resveratrol is well known to exhibit vascular relaxant and antihypertensive effects. In this study, we determined the effects of resveratrol on the modulation of cytosolic [Ca²⁺] level and adenosine 5′-Triphosphate-induced Ca²⁺release from the sarcoplasmic reticulum (SR) in rat aortic smooth muscle cells (ASMCs) and explored its underlying mechanisms. In this article, cytosolic [Ca²⁺] and SR [Ca²⁺] in ASMCs were determined by Fluo-4/acetoxymethyl and Mag-Fluo-4/acetoxymethyl respectively. Resveratrol (20, 50, and 100 µM) caused a rapid and substantial reduction in cytosolic [Ca²⁺] in ASMCs bathed in normal Hank's Balanced Salt Solution or Ca²⁺-free Hank's Balanced Salt Solution. Pretreatment with resveratrol reduced adenosine 5′-Triphosphate-induced SR Ca²⁺release and SR Ca²⁺content. In the cells bathed in Na⁺-free physiological saline, which favors the reverse mode of the Na⁺-Ca²⁺exchanger (NCX), resveratrol induced an increase in cytosolic [Ca²⁺] and SR [Ca²⁺]. However, its effect on cytosolic [Ca²⁺] was inhibited by the selective NCX inhibitor, SEA0400. Our findings suggest that resveratrol reduces cytosolic [Ca²⁺] and SR [Ca²⁺] in ASMCs in normal physiological saline, which might be, at least in part, mediated by the NCX.