Nicorandil-induced ATP release in endothelial cells of rat caudal artery is associated with increase in intracellular Ca2+

The effect of nicorandil, an ATP-sensitive K+ channel opener, on the level of intracellular Ca2+ ([Ca2+](i)) and on ATP release in endothelial cells of the rat caudal artery was examined using a fluorescent confocal microscopic imaging system and high-performance liquid chromatography (HPLC) with fluorescent detection, respectively. Nicorandil significantly increased [Ca2+](i) and the overflow of ATP and its metabolites. The former reaction was abolished in the absence of extracellular Ca2+, but it did not change in the presence of thapsigargin or cycIopiazonic acid. The increase in the overflow of ATP and [Ca2+](i) induced by nicorandil was markedly suppressed by glibenclamide, an ATP-sensitive K+ channel blocker. The increase of [Ca2+](i) induced by nicorandil was significantly and inversely correlated with the level of intracellular ATP in the endothelial cells, suggesting that activation of ATP-sensitive K+ channels by nicorandil increases Ca2+ influx in endothelial cells. The increase of [Ca2+](i) might be associated with ATP release. (C) 2001 Elsevier Science B.V. All rights reserved.