Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.

中文翻译：

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小胶质细胞衍生的 NLRP3 激活介导肾素原在应激诱导的高血压大鼠的延髓腹外侧的升压作用。

自主脑区（如延髓腹外侧（RVLM））内小胶质细胞激活和神经炎症的增加与应激性高血压（SIH）有关。Prorenin 是脑肾素-血管紧张素系统 (RAS) 的成员，可以直接激活小胶质细胞。本研究旨在研究肾素原对 SIH 大鼠 RVLM 小胶质细胞活化的影响。大鼠接受间歇性电足电击加噪音，连续 15 天每天两次，每次 2 小时，并监测平均动脉压 (MAP) 和肾交感神经活动 (RSNA)。结果显示 MAP 和 RSNA 增加，这与促炎表型 (M1) 转换增加并行。在 SIH 大鼠的 RVLM 中，肾素原及其受体 (PRR) 表达和含有 3 的 NLR 家族 pyrin 结构域 (NLRP3) 激活增加。此外，PLX5622（一种小胶质细胞耗竭剂）、MCC950（一种 NLRP3 抑制剂）和/或 PRO20（一种（原）肾素受体拮抗剂）对大鼠具有抗高血压作用。在用 PLX5622 治疗的 SIH 大鼠中，RVLM 中的 NLRP3 表达降低。Mito-tracker 染色显示 NLRP3 从线粒体转移到肾素原刺激的小胶质细胞中的细胞质。Prorenin 增加了 ROS 触发的 M1 表型转换和 NLRP3 激活，而 MCC950 减少了 M1 极化。总之，RVLM 中上调的肾素原可能参与了 SIH 的发病机制，由小胶质细胞衍生的 NLRP3 炎症小体的激活介导。