Development of nitric oxide donors for the treatment of cardiovascular diseases.
Development of nitric oxide donors for the treatment of cardiovascular diseases.
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DOI：
10.2174/187152507781058735
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发表时间：
2007-06
影响因子：
--
通讯作者：
H. Katsumi;M. Nishikawa;M. Hashida
中科院分区：
文献类型：
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作者：
H. Katsumi;M. Nishikawa;M. Hashida
一氧化氮(NO)是一种动态调节心血管系统生理功能的分子，包括血管平滑肌松弛、抑制血小板聚集和调节免疫反应。由于NO水平降低与多种疾病的发生和发展有关，NO有望在心血管疾病的治疗中发挥作用，如高血压、中风、冠状动脉疾病、动脉粥样硬化、经皮冠状动脉腔内成形术后的血小板聚集和缺血/再灌注损伤。到目前为止，可以在体内释放NO的药理活性化合物，如有机硝酸盐和硝普钠，已经被用作治疗药物，但它们的疗效受到NO释放速度快、在靶点分布不佳、毒性和诱导耐受的严重限制。因此，具有更好药理和药代动力学特性的新的NO供体将是非常可取的。在这篇综述中，总结了在开发新的无捐赠者和无递送系统方面的最新挑战。此外，还讨论了新型NO供体的未来发展，以期优化NO在心血管疾病治疗中的应用。
Nitric oxide (NO) is a molecule that dynamically modulates the physiological functions of the cardiovascular system, which include relaxation of vascular smooth muscle, inhibition of platelet aggregation, and regulation of immune responses. Because a reduced NO level has been implicated in the onset and progression of various disease states, NO is expected to provide therapeutic benefits in the treatment of cardiovascular diseases, such as essential hypertension, stroke, coronary artery disease, atherosclerosis, platelet aggregation after percutaneous transluminal coronary angioplasty, and ischemia/reperfusion injury. To date, pharmacologically active compounds that can release NO within the body, such as organic nitrates and sodium nitroprusside, have been used as therapeutic agents, but their efficacy is significantly limited by their rapid NO release, poor distribution to the target site, toxicity, and induction of tolerance. Therefore, new NO donors with better pharmacological and pharmacokinetic properties would be highly desirable. In this review, recent challenges in the development of new NO donors and NO delivery systems are summarized. Then, future developments of novel NO donors are also discussed in order to optimize NO delivery in the treatment of cardiovascular diseases.