Dipyridamole inhibits intracellular calcium transients in isolated rat arteriole smooth muscle cells.
Dipyridamole inhibits intracellular calcium transients in isolated rat arteriole smooth muscle cells.
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DOI：
10.1679/aohc.71.235
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发表时间：
2008-12
影响因子：
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通讯作者：
T. Saino;Toshinari Misaki;M. Matsuura;T. Shikanai;Y. Satoh
中科院分区：
文献类型：
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作者：
T. Saino;Toshinari Misaki;M. Matsuura;T. Shikanai;Y. Satoh
双嘧达莫是腺苷摄取抑制剂和cGMP磷酸二酯酶抑制剂，常用于心绞痛患者的预防性治疗。然而，双嘧达莫对全身血管，特别是外周血管系统的影响还不清楚。因此，双嘧达莫对ATP诱导的小动脉收缩的影响，特别是参考细胞内Ca（2+）浓度（[Ca（2+）]（i）），使用实时共聚焦显微镜检查。在0.1- 10 μ M范围内，潘生丁仅引起睾丸和脑小动脉平滑肌细胞[Ca（2+）]（i）轻微降低。然而，100 μ M双嘧达莫诱导细胞内[Ca（2+）]（i）显著降低。在10 μ M双嘧达莫存在下，ATP诱导的睾丸小动脉平滑肌细胞[Ca（2+）]（i）的变化被抑制，但在脑小动脉平滑肌细胞中不受抑制。此外，α，β-亚甲基ATP诱导的睾丸小动脉平滑肌细胞[Ca（2+）]（i）增加也部分抑制双嘧达莫的存在。当睾丸小动脉灌注潘生丁时，没有检测到一氧化氮水平的增加。高水平的K（+）诱导睾丸小动脉[Ca（2+）]（i）增加，这也被潘生丁部分抑制。在存在影响蛋白激酶A或G的物质的情况下，ATP诱导的[Ca（2+）]（i）未被完全抑制。这些结果表明，双嘧达莫可能不仅作为腺苷摄取的抑制剂和cGMP磷酸二酯酶抑制剂，而且作为钙通道阻滞剂在小动脉平滑肌细胞。
Dipyridamole, an inhibitor of adenosine uptake as well as a cGMP phosphodiesterase inhibitor, is commonly used in prophylactic therapy for patients with angina pectoris. However, the effects of dipyridamole on systemic blood vessels, especially on the peripheral vascular system, are not well understood. Therefore, the effect of dipyridamole on ATP-induced arteriole contraction was examined with special reference to intracellular Ca(2+) concentration ([Ca(2+)](i)) using real-time confocal microscopy. In cases of 0.1-10microM range, dipyridamole induced only slight [Ca(2+)](i) decreases in smooth muscle cells of both testicular and cerebral arterioles. However, 100microM dipyridamole induced substantial [Ca(2+)](i) decreases in the cells. In the presence of 10microM dipyridamole, changes in ATP-induced [Ca(2+)](i) were found to be inhibited in smooth muscle cells of testicular arterioles but not in those of cerebral arterioles. In addition, alpha, beta-methylene ATP-induced [Ca(2+)](i) increases in testicular arteriole smooth muscle cells were also partially inhibited in the presence of dipyridamole. When testicular arterioles were perfused with dipyridamole, no increases in nitric oxide levels were detected. High levels of K(+) induced a [Ca(2+)](i) increase in testicular arterioles that was also partially inhibited by dipyridamole. In the presence of substances that affect protein kinase A or G, ATP-induced [Ca(2+)](i) was not completely inhibited. These findings suggest that dipyridamole may act not only as an inhibitor of adenosine uptake and as a cGMP phosphodiesterase inhibitor, but also as a calcium channel blocker in arteriole smooth muscle cells.