从神经角度看高血压的治疗:高血压的神经网络兴奋和抑制(E/I)失衡

IF 2.8 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Min Xia, Tianyu Wang, Yizhu Wang, Tingting Hu, Defang Chen, Bin Wang
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引用次数: 0

摘要

尽管已开发出越来越多的抗高血压药物并应用于临床,但仍存在持续的不足,包括终身剂量、联合疗法等问题。尽管在克服这些不足的情况下接受了治疗,但每 5 名患者中仍有约 4 人无法获得可靠的血压(BP)控制。在高血压的治疗中应用神经调控技术是一种开创性的治疗策略,同时也暗示了高血压发病的潜在中枢神经机制。我们假设,神经网络是维持适当神经功能的重要组成部分,与高血压有关。根据同行评审的研究和我们的实验室调查,我们努力研究高血压的潜在神经机制,确定高血压发病与兴奋和抑制(E/I)失衡之间的密切关系。除了兴奋性谷氨酸能和 GABAergic 抑制系统的参与,高血压的发病机制还与电压门控钠通道(VGSCs,Nav)介导的 E/I 平衡有关。谷氨酸的超载或谷氨酸受体的增强可能是E/I失衡的原因,最终引发高血压。GABA 缺失和 GABA 受体功能障碍也被证明与此有关。此外,我们还发现钠通道表达和功能异常会改变神经兴奋性,从而扰乱E/I平衡,并可能成为高血压的潜在机制。这些发现有望为创新抗高血压疗法的发展提供潜在策略,并为探索抗高血压药物的中枢神经系统(CNS)靶点提供有意义的参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A neural perspective on the treatment of hypertension: the neurological network excitation and inhibition (E/I) imbalance in hypertension
Despite the increasing number of anti-hypertensive drugs have been developed and used in the clinical setting, persistent deficiencies persist, including issues such as lifelong dosage, combination therapy. Notwithstanding receiving the treatment under enduring these deficiencies, approximately 4 in 5 patients still fail to achieve reliable blood pressure (BP) control. The application of neuromodulation in the context of hypertension presents a pioneering strategy for addressing this condition, con-currently implying a potential central nervous mechanism underlying hypertension onset. We hypothesize that neurological networks, an essential component of maintaining appropriate neurological function, are involved in hypertension. Drawing on both peer-reviewed research and our laboratory investigations, we endeavor to investigate the underlying neural mechanisms involved in hypertension by identifying a close relationship between its onset of hypertension and an excitation and inhibition (E/I) imbalance. In addition to the involvement of excitatory glutamatergic and GABAergic inhibitory system, the pathogenesis of hypertension is also associated with Voltage-gated sodium channels (VGSCs, Nav)-mediated E/I balance. The overloading of glutamate or enhancement of glutamate receptors may be attributed to the E/I imbalance, ultimately triggering hypertension. GABA loss and GABA receptor dysfunction have also proven to be involved. Furthermore, we have identified that abnormalities in sodium channel expression and function alter neural excitability, thereby disturbing E/I balance and potentially serving as a mechanism underlying hypertension. These insights are expected to furnish potential strategies for the advancement of innovative anti-hypertensive therapies and a meaningful reference for the exploration of central nervous system (CNS) targets of anti-hypertensives.
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来源期刊
Frontiers in Cardiovascular Medicine
Frontiers in Cardiovascular Medicine Medicine-Cardiology and Cardiovascular Medicine
CiteScore
3.80
自引率
11.10%
发文量
3529
审稿时长
14 weeks
期刊介绍: Frontiers? Which frontiers? Where exactly are the frontiers of cardiovascular medicine? And who should be defining these frontiers? At Frontiers in Cardiovascular Medicine we believe it is worth being curious to foresee and explore beyond the current frontiers. In other words, we would like, through the articles published by our community journal Frontiers in Cardiovascular Medicine, to anticipate the future of cardiovascular medicine, and thus better prevent cardiovascular disorders and improve therapeutic options and outcomes of our patients.
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