Wang Renjun, Wang Min, Du Dongshu, Shan Zhiying, Bi Lanrong, Chen Qing-Hui
Department of Biotechnology, School of Life Science, Jilin Normal University, Siping 136000, China.
Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI 49931-1200, USA.
Antioxidants (Basel). 2025 Mar 28;14(4):408. doi: 10.3390/antiox14040408.
Hypertension (HTN) is a complex disease with significant global health implications, driven by neural and oxidative mechanisms. Reactive oxygen species (ROS), once considered mere metabolic byproducts, are now recognized as one of the key contributors to dysfunction of the autonomic nerve system, which involves the onset and progression of HTN. This review highlights the dynamic roles of ROS in neuronal signaling, subcellular compartmentalization, and brain-immune interactions, focusing on their impacts on synaptic remodeling, neuroinflammation, and epigenetic modifications within key autonomic regions such as the paraventricular nucleus and rostral ventrolateral medulla. We discuss novel ROS sources, including microglia-derived and endoplasmic reticulum stress-related ROS, and their contributions to HTN. Subcellular dynamics, such as ROS signaling at mitochondria-associated membranes and neuronal microdomains, are explored as activators of the sympathetic nerve system. Emerging evidence has linked ROS to epigenetic regulation, including histone modifications and non-coding RNA expression, with sex-specific differences offering insights for the development of personalized therapies. Innovative therapeutic strategies targeting ROS involve precision delivery systems, subcellular modulators, and circadian-optimized antioxidants. We propose several priorities for future research, including the real-time imaging of brain ROS, translating preclinical findings into clinical applications, and leveraging precision medicine to develop tailored interventions based on ROS activity and genetic predisposition. Through emphasizing the spatial and temporal complexity of ROS in HTN, this review identifies novel therapeutic opportunities and establishes a foundation for targeted treatments to address this health challenge.
高血压（HTN）是一种复杂的疾病，对全球健康具有重大影响，由神经和氧化机制驱动。活性氧（ROS）曾被认为只是代谢副产物，现在被认为是自主神经系统功能障碍的关键因素之一，自主神经系统功能障碍涉及高血压的发生和发展。本综述强调了ROS在神经元信号传导、亚细胞区室化和脑-免疫相互作用中的动态作用，重点关注它们对关键自主神经区域如室旁核和延髓头端腹外侧的突触重塑、神经炎症和表观遗传修饰的影响。我们讨论了新的ROS来源，包括小胶质细胞衍生的ROS和内质网应激相关的ROS，以及它们对高血压的影响。探索了亚细胞动力学，如线粒体相关膜和神经元微区的ROS信号传导，作为交感神经系统的激活剂。新出现的证据将ROS与表观遗传调控联系起来，包括组蛋白修饰和非编码RNA表达，性别特异性差异为个性化治疗的发展提供了见解。针对ROS的创新治疗策略包括精准递送系统、亚细胞调节剂和昼夜节律优化的抗氧化剂。我们提出了未来研究的几个重点，包括脑ROS的实时成像、将临床前研究结果转化为临床应用，以及利用精准医学根据ROS活性和遗传易感性制定量身定制的干预措施。通过强调ROS在高血压中的时空复杂性，本综述确定了新的治疗机会，并为应对这一健康挑战的靶向治疗奠定了基础。
