Trans ‐ and cis ‐resveratrol increase cytoplasmic calcium levels in A7r5 vascular smooth muscle cells

The effects of trans ‐ and cis ‐resveratrol on cytosolic Ca 2+ concentration ([Ca 2+ ] i ) were studied using fura‐2 in vascular smooth muscle cells (A7r5). Both isomers of resveratrol caused a sustained elevation in [Ca 2+ ] i , cis ‐resveratrol being significantly more effective than the trans‐ isomer. The resveratrol‐induced increase in [Ca 2+ ] i was significantly potentiated by the previous application of low concentrations of thapsigargin, partially inhibited by nifedipine or Ni 2+ , and not affected by SKF 96365. In the absence of extracellular Ca 2+ , both isomers of resveratrol induced a transient, slow increase in [Ca 2+ ] i , which was inhibited by the previous depletion of intracellular stores with thapsigargin and completely blocked by preincubation with TMB‐8, an inhibitor of intracellular calcium release. Reintroduction of Ca 2+ in the external solution after the resveratrol‐induced release of Ca 2+ activated the Ca 2+ influx through store‐operated calcium channels. The resveratrol‐induced increase in [Ca 2+ ] i in the absence of extracelullar Ca 2+ partially reduced the increase in [Ca 2+ ] i evoked by the subsequent application of thapsigargin. Our results suggest that trans ‐ and cis ‐resveratrol induce a depletion of Ca 2+ from the same intracellular stores released by thapsigargin and subsequent capacitative influx of Ca 2+ . Additionally, a direct activation of transmembrane Ca 2+ influx through another type of channel may be also implicated.