Post-traumatic stress disorder (PTSD), an anxiety-related syndrome, is associated with increased risk for cardiovascular diseases. The present study investigated whether predator scent (PS) stress, a model of PTSD, induces sensitization of hypertension and anxiety-like behaviors and underlying mechanisms related to renin–angiotensin systems (RAS) and inflammation. Coyote urine, as a PS stressor, was used to model PTSD. After PS exposures, separate cohorts of rats were studied for hypertensive response sensitization (HTRS), anxiety-like behaviors, and changes in plasma levels and mRNA expression of several components of the RAS and proinflammatory cytokines (PICs) in the lamina terminalis (LT), paraventricular nucleus (PVN), and amygdala (AMY). Rats exposed to PS as compared to control animals exhibited (1) a significantly greater hypertensive response (i.e., HTRS) when challenged with a slow-pressor dose of angiotensin (ANG) II, (2) significant decrease in locomotor activity and increase in time spent in the closed arms of a plus maze as well as general immobility (i.e., behavioral signs of increased anxiety), (3) upregulated plasma levels of ANG II and interleukin-6, and (4) increased expression of message for components of the RAS and PICs in key brain nuclei. All the PS-induced adverse effects were blocked by pretreatment with either an angiotensin-converting enzyme antagonist or a tumor necrosis factor-α inhibitor. The results suggest that PS, used as an experimental model of PTSD, sensitizes ANG II-induced hypertension and produces behavioral signs of anxiety, probably through upregulation of RAS components and inflammatory markers in plasma and brain areas associated with anxiety and blood pressure control.

创伤后应激障碍（PTSD）是一种与焦虑相关的综合症，与心血管疾病的风险增加有关。本研究调查了捕食者气味（PS）应激（一种 PTSD 模型）是否会诱发高血压和焦虑样行为的敏感性，以及与肾素-血管紧张素系统（RAS）和炎症相关的潜在机制。土狼尿液作为 PS 应激源，被用来模拟 PTSD。PS暴露后，对不同组的大鼠进行了高血压反应敏化（HTRS）、焦虑样行为以及血浆水平和终板（LT）中RAS和促炎细胞因子（PIC）几种成分的mRNA表达的变化的研究、室旁核（PVN）和杏仁核（AMY）。与对照动物相比，暴露于 PS 的大鼠表现出 (1) 当接受缓慢升压剂量的血管紧张素 (ANG) II 挑战时，显着增强高血压反应（即 HTRS），(2) 运动活动显着降低，时间增加在十字迷宫的封闭臂中度过以及一般不动（即焦虑增加的行为迹象），（3）ANG II和白细胞介素6的血浆水平上调，以及（4）关键脑核中的 RAS 和 PIC。所有 PS 引起的不良反应均可通过血管紧张素转换酶拮抗剂或肿瘤坏死因子-α 抑制剂预处理来阻断。结果表明，PS 作为 PTSD 的实验模型，可能通过上调血浆和大脑区域中与焦虑和血压控制相关的 RAS 成分和炎症标志物，使 ANG II 诱导的高血压变得敏感并产生焦虑的行为迹象。