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

The effects of trans- and cis-resveratrol on cytosolic Ca2+ concentration ([Ca2+](i)) were studied using fura-2 in vascular smooth muscle cells (A7r5). Both isomers of resveratrol caused a sustained elevation in [Ca2+](i), cis-resveratrol being significantly more effective than the trans-isomer. The resveratrol-induced increase in[Ca2+](i) was significantly potentiated by the previous application of low concentrations of thapsigargin, partially inhibited by nifedipine or Ni2+, and not affected by SKF 96365. In the absence of extracellular Ca2+, both isomers of resveratrol induced a transient, slow increase in [Ca2+](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 Ca2+ in the external solution after the resveratrol-induced release of Ca2+ activated the Ca2+ influx through store-operated calcium channels. The resveratrol-induced increase in [Ca2+](i) in the absence of extracelullar Ca2+ partially reduced the increase in [Ca2+](i) evoked by the subsequent application of thapsigargin. Our results suggest that trans- and cis-resveratrol induce a depletion of Ca2+ from the same intracellular stores released by thapsigargin and subsequent capacitative influx of Ca2+. Additionally, a direct activation of transmembrane Ca2+ influx through another type of channel may be also implicated.