Nicorandil enhances the effect of endothelial nitric oxide under hypoxia–reoxygenation: Role of the KATPatp" were changed to "KATP". Please check.--> channel

Nicorandil increased the anti-platelet aggregation activity of endothelial cells when endothelial cells were exposed to hypoxia–reoxygenation conditions. However, nicorandil (0.1–10 μM) did not inhibit platelet aggregation directly. The mechanism by which nicorandil increases the anti-aggregation activity of hypoxia–reoxygenation treated endothelial cells was investigated. The effect of nicorandil was observed even in indomethacin-treated endothelial cells, but the effect was eliminated by treating endothelial cells with NG-nitro-l-arginine methyl ester (L-NAME). This indicates that nicorandil enhances the anti-aggregation activity of endothelial nitric oxide (NO). Nicorandil did not increase the anti-aggregation activity of endothelial NO when endothelial cells were pre-treated with superoxide dismutase or 4-(2-aminophenyl)-benzenesulfonyl fluoride, an inhibitor of NADPH oxidase. Nicorandil dose-dependently inhibited the reactive oxygen species generation induced by an oxidative stress in endothelial cells. The effect of nicorandil on anti-aggregation activity was abrogated by glibenclamide, an ATP-sensitive potassium (KATP) channel blocker. Pinacidil, a KATP channel opener, also enhanced the anti-aggregation activity of endothelial NO. This effect was similarly abrogated by glibenclamide. These results suggest that nicorandil may inhibit the generation of superoxide (O2−) from hypoxia–reoxygenation treated endothelial cells through activation of the KATP channel, and that nicorandil may prevent the disappearance of endothelial NO by O2−.