尼可地尔降低血管平滑肌细胞内ATP诱导的游离钙浓度

Nicorandil inhibits ATP-induced cytosolic free calcium increase in cultured vascular smooth muscle cells

目的：探讨尼可地尔对血管平滑肌细胞内游离钙（［Ｃａ２＋］ｉ）的影响及机理。方法：培养的兔主动脉平滑肌细胞加入Ｆｕｒａ－２ＡＭ２５μｍｏｌ／Ｌ，在３７℃下孵育５０ｍｉｎ，［Ｃａ２＋］ｉ用荧光分光光度计检测。结果：ＡＴＰ（０１ｍｍｏｌ／Ｌ）诱导的［Ｃａ２＋］ｉ峰相和持续相增加可被尼可地尔抑制，且呈剂量依赖性，尼可地尔（１０μｍｏｌ／Ｌ）的抑制作用可被优降糖（１０μｍｏｌ／Ｌ）完全阻断（峰相：５３０±３１ｖｓ５４４±４１ｎｍｏｌ／Ｌ，持续相：３７０±１９ｖｓ３８１±１１ｎｍｏｌ／Ｌ，Ｐ＞００５）；在无钙溶液中，先给尼可地尔能显著抑制ＡＴＰ诱导的［Ｃａ２＋］ｉ峰相增加。结论：尼可地尔抑制ＡＴＰ诱导的［Ｃａ２＋］ｉ增加，可能与减少细胞外钙内流及细胞内钙释放有关。

AIM:To study the effects of nicorandil on cytosolic free calcium([Ca 2+ ] i) changes and their possible mechanisms in vascular smooth muscle cells.METHODS:Cultured rabbit aortic smooth muscle cells were treated with Fura-2 AM 2.5 μmol·L 1 at 37℃ for 50 min.[Ca 2+ ] i level was measured by fluorospectrometer.RESULTS:ATP (0.1 mmol·L 1 )-induced peak and sustained phase [Ca 2+ ] i increase were inhibited by nicorandil in a concentration-dependent manner. The effects of nicorandil(10 μmol·L 1 ) was completely canceled (peak phase:530±31 vs 544±41 nmol·L 1 ; sustained phase: 370±19 vs 381±11 nmol·L 1 ) by glibenclamide (10 μmol·L 1 ). Pretreated with the nicorandil, the peak [Ca 2+ ] i elevation induced by ATP was reduced in the Ca 2+ -free solution (140±22 vs 260±33 nmol·L 1 , P <0 01).CONCLUSION:Nicorandil inhibits ATP-induced[Ca 2+ ] i increase, associated with the decreases of both Ca 2+ release from intracellular store and Ca 2+ influs from extracellular store.