Effects of trans- and cis-resveratrol on Ca2+ handling in A7r5 vascular myocytes

Although the natural polyphenol resveratrol posses a direct vasorelaxant effect, its effects on cytoplasmic Ca2+ concentration ([Ca2+]i) in vascular cells remain still unclear. Here, we have investigated the effects of the isomers trans- and cis-resveratrol on agonist- and high-K+-induced [Ca2+]i increases and on voltage-activated transmembrane Ca2+ fluxes using imaging and patch-clamp techniques in vascular A7r5 myocytes. Arginine vasopressin (AVP) or angiotensin II caused a biphasic increase in [Ca2+]i that was reduced by preincubation with trans-resveratrol and cis-resveratrol. Both isomers also reduced the agonist-induced increase in [Ca2+]i in absence of extracellular Ca2+. In high-K+ Ca2+-free solution, reintroduction of Ca2+ caused a sustained rise in [Ca2+]i that was reduced by preincubation with trans-resveratrol or cis-resveratrol. When the isomers were applied during the plateau phase of the agonist- or the high-K+-induced response, a biphasic change in [Ca2+]i was observed: a transient reduction of the plateau (< 5 min) followed by an increase (> 10 min). Finally, trans-resveratrol and cis-resveratrol inhibited voltage-dependent L-type Ca2+ currents (ICa(L)). In conclusion, resveratrol isomers exert a dual effect on [Ca2+]i handling in A7r5 myocytes: 1) a blockade of ICa(L) and 2) an increase in [Ca2+]i by depletion of intracellular Ca2+ stores (which interferes with the agonist-induced release of intracellular Ca2+) and influx of Ca2+, mainly due to activation of capacitative Ca2+ entry, although other Ca2+-permeable channels are also involved. Taken together, these effects may explain, in part, the endothelium-independent vasorelaxant effects of resveratrol in rat aorta.