Yan Jiu-Qiong, Huang Fang, Hao Fan, Su Xiao-Ling, Meng Qi, Xu Ming-Juan
Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Department of Geriatics, Jinling Hospital, Nanjing, China.
Front Physiol. 2017 Oct 4;8:772. doi: 10.3389/fphys.2017.00772. eCollection 2017.
It has been demonstrated that preeclampsia, a pregnancy-specific hypertension disorder, is characterized by high blood pressure (BP) and sympathetic overactivity. Increased reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM), a key region for controlling sympathetic tone, has been reported to contribute to high level of BP and sympathetic outflow. The aim of the present study was to determine the role of the RVLM ROS in mediating the preeclampsia-associated cardiovascular dysfunction. The animal model of preeclampsia was produced by administration of desoxycorticosterone acetate (DOCA) to pregnant rats. Compared with normal pregnant rats without DOCA treatment (NP), the protein concentration and norepinephrine excretion in 24-h urine, as well as BP in pregnant rats with DOCA treatment (PDS) were significantly increased. The levels of superoxide anion and the protein expression of NADPH oxidase subtype (NOX4) in the RVLM were significantly increased in PDS than in NP groups. Furthermore, microinjection of the superoxide dismutase (SOD) mimic Tempol (5 nmol) into the RVLM significantly decreased BP, heart rate, and renal sympathetic never activity in PDS but not in NP group. The present data suggest that high BP and sympathetic overactivity in preeclampsia rats is associated with increased oxidative stress in the RVLM via upregulation of NOX4 expression.
子痫前期是一种妊娠特异性高血压疾病,已证实其特征为高血压(BP)和交感神经过度活跃。延髓头端腹外侧区(RVLM)是控制交感神经张力的关键区域,据报道该区域活性氧(ROS)增加会导致血压升高和交感神经输出增加。本研究的目的是确定RVLM中的ROS在介导子痫前期相关心血管功能障碍中的作用。通过给妊娠大鼠注射醋酸脱氧皮质酮(DOCA)建立子痫前期动物模型。与未接受DOCA治疗的正常妊娠大鼠(NP)相比,接受DOCA治疗的妊娠大鼠(PDS)的24小时尿蛋白浓度和去甲肾上腺素排泄量以及血压均显著升高。PDS组RVLM中超氧阴离子水平和NADPH氧化酶亚型(NOX4)的蛋白表达均显著高于NP组。此外,向RVLM中微量注射超氧化物歧化酶(SOD)模拟物Tempol(5 nmol)可显著降低PDS组的血压、心率和肾交感神经活性,但对NP组无此作用。目前的数据表明,子痫前期大鼠的高血压和交感神经过度活跃与RVLM中通过上调NOX4表达而增加的氧化应激有关。