Chen Xinqian, Yan Xin, Yu Chunxiu, Chen Qing-Hui, Bi Lanrong, Shan Zhiying
Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI 49931, USA.
Health Research Institute, Michigan Technological University, Houghton, MI 49931, USA.
Antioxidants (Basel). 2024 Nov 20;13(11):1423. doi: 10.3390/antiox13111423.
This study investigates the impact of single prolonged stress (SPS), a model of post-traumatic stress disorder (PTSD), on cardiovascular responses, hypothalamic paraventricular nucleus (PVN) activity, and vascular function to elucidate the mechanisms linking traumatic stress to hypertension. Although SPS did not directly cause chronic hypertension in male Sprague Dawley (SD) rats, it induced acute but transient increases in blood pressure and heart rate and significantly altered the expression of hypertension-associated genes, such as vasopressin, angiotensin II type 1 receptor (AT1R), and FOSL1 in the PVN. Notably, mitochondrial reactive oxygen species (mtROS) were predominantly elevated in the pre-autonomic regions of the PVN, colocalizing with AT1R- and FOSL1-expressing cells, suggesting that oxidative stress may amplify sympathetic activation and stress responses. SPS also increased mRNA levels of pro-inflammatory cytokines (TNFα and IL1β) and inducible nitric oxide synthase (iNOS) in the aorta, and impaired vascular reactivity to vasoconstrictor and vasodilator stimuli, reflecting compromised vascular function. These findings suggest that SPS-sensitize neuroendocrine, autonomic, and vascular pathways create a state of cardiovascular vulnerability that could predispose individuals to hypertension when exposed to additional stressors. Understanding these mechanisms provides critical insights into the pathophysiology of stress-related cardiovascular disorders and underscores the need for targeted therapeutic interventions that address oxidative stress and modulate altered PVN pathways to mitigate the cardiovascular impact of PTSD and related conditions.
本研究调查了创伤后应激障碍（PTSD）模型——单次长时间应激（SPS）对心血管反应、下丘脑室旁核（PVN）活动及血管功能的影响，以阐明创伤性应激与高血压之间的联系机制。尽管SPS未直接导致雄性Sprague Dawley（SD）大鼠出现慢性高血压，但它引起了血压和心率的急性但短暂升高，并显著改变了PVN中与高血压相关基因的表达，如血管加压素、血管紧张素II 1型受体（AT1R）和FOSL1。值得注意的是，PVN的自主神经前区线粒体活性氧（mtROS）主要升高，与表达AT1R和FOSL1的细胞共定位，提示氧化应激可能增强交感神经激活和应激反应。SPS还增加了主动脉中促炎细胞因子（TNFα和IL1β）和诱导型一氧化氮合酶（iNOS）的mRNA水平，并损害了血管对血管收缩剂和血管舒张剂刺激的反应性，反映出血管功能受损。这些发现表明，SPS使神经内分泌、自主神经和血管通路敏感化，从而造成一种心血管易损状态，当个体暴露于额外应激源时可能易患高血压。了解这些机制为应激相关心血管疾病的病理生理学提供了关键见解，并强调需要有针对性的治疗干预措施，以解决氧化应激问题并调节PVN通路改变，从而减轻PTSD及相关病症对心血管的影响。
