Reply to Harris et al.: Differential impacts of omega-3 fatty acids and their derivatives on blood pressure.
Reply to Harris et al.: Differential impacts of omega-3 fatty acids and their derivatives on blood pressure.
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回复 Harris 等人：omega-3 脂肪酸及其衍生物对血压的不同影响。
DOI：
10.1073/pnas.1305790110
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发表时间：
2013
影响因子：
11.1
通讯作者：
Hou,Shangwei
中科院分区：
文献类型：
--
作者：
Hoshi,Toshinori;Wissuwa,Bianka;Tian,Yutao;Tajima,Nobuyoshi;Xu,Rong;Bauer,Michael;Heinemann,StefanH;Hou,Shangwei
在我们的论文(1)中，我们介绍了一项仔细对照的研究结果，表明二十二碳六烯酸(DHA)在急性应用时，激活大电导钙通道和电压激活的K+(BK)通道，并降低血压。我们发现，各种omega-3脂肪酸、omega-6脂肪酸及其衍生物在急性应用时对血压和BK通道有显著不同的影响。我们不会就omega-3脂肪酸在临床上的使用或作为营养补充剂提供任何具体的建议或建议。然而，我们注意到高血压是公认的死亡风险因素，在美国，许多人死于相关的并发症。在护理危重病人时，重要组织的灌注压是一个关键问题，血压的任何下降都可能是不可容忍的。Omega-3脂肪酸和其他“免疫营养素”对普通人群和危重患者的作用已经引起了相当大的关注；然而，关于它们的影响或结果的研究产生了非常有争议的结果。正如Harris等人所说(2)，脂肪酸的新陈代谢是一个复杂的问题。我们的结构-活性实验结果突出了各种omega-3脂肪酸、omega-6脂肪酸及其衍生物的显著对比效果。结果表明，DHA的乙酯不能兴奋BK通道，对血压无影响。这一发现表明，该药物和其他衍生物(如甘油酯)口服或非肠道给药的影响需要在临床研究中进行严格的测试。此外，健康人和危重病人对各种脂肪酸的生理反应可能会有明显的不同。我们的结果强调了在讨论omega-3脂肪酸和鱼油时正确指定准确分子的重要性。我们希望我们的机制结果涵盖多个水平的生理组织，从整个动物到BK通道蛋白的单一定义的动力学转变，以及那些使用人类受试者的研究提供的信息，以及Harris等人的信件，将对其他科学家和临床医生得出他们自己的应用结论有用。
In our paper (1), we present the results of a carefully controlled study demonstrating that docosahexaenoic acid (DHA) activated largeconductance Ca2+-and voltage-activated K+(BK) channels and lowered blood pressure when applied acutely. We showed that various omega-3 fatty acids, omega-6 fatty acids, and their derivatives had remarkably different effects on blood pressure and BK channels when acutely applied. We do not offer any specific recommendation or advice as to the use of omega-3 fatty acids for clinical situations or as nutritional supplements. However, we note that hypertension is a well-recognized mortality risk factor and many in the United States die from related complications. In caring for the critically ill, perfusion pressure of vital tissues is a key concern and any decrease in blood pressure may not be tolerated. Considerable attention has been paid to the role of omega-3 fatty acids and other “immunonutrients” for the general population and critically ill patients; however, studies have yielded very controversial results regarding their impact or outcome. As stated by Harris et al.(2), the metabolism of fatty acids is a complex issue. The results of our structure-activity experiments highlighted remarkably contrasting effects of various omega-3 fatty acids, omega-6 fatty acids, and their derivatives. In particular, the results presented in the article showed that the ethyl ester of DHA failed to stimulate BK channels and had no effect on blood pressure. This finding suggests that the impact of this and other derivatives (such as the glycerolester) administered either orally or parenterally requires rigorous testing in clinical studies. In addition, the physiological responses of healthy individuals and critically ill patients to various fatty acids may differ appreciably. Our results emphasized the importance of properly specifying exact molecules whenever omega-3 fatty acids and fish oil are discussed. We hope that our mechanistic results encompassing multiple levels of physiological organization, from whole animals down to a single defined kinetic transition of the BK channel protein, along with the information provided by those studies using human subjects, as well as the Letter by Harris et al., will be useful for other scientists and clinicians to draw their conclusions for their own applications.