Zhang Qi, Tan Yingying
Medical Research Experimental Center, Shaanxi University of Chinese Medicine, Xianyang 712046, China. E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2014 Nov;34(11):1632-6.
To investigate whether brain reactive oxygen species mediate sympathoexcitation and arterial pressure elevation in DOCA-salt hypertensive rats.
DOCA-salt hypertensive model was established in male SD rats by subcutaneous injection of DOCA after uninephrectomy and drinking 1% NaCl solution for 4 weeks. The baseline mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in the rats under mild anesthesia, and MAP changes following intravenous hexamethonium injection were observed. The responses of MAP, HR and RSNA to intracerebroventricular administration of tempol (20 µmol/L in 10 µl) were evaluated; plasma NE level was measured with ELISA, and ROS level and NAD(P)H oxidase activity in the hypothalamus were detected using chemiluminescence assay.
MAP and plasma NE levels were significantly increased in DOCA-salt rats as compared with those in the control group (P<0.01). In DOCA-salt hypertensive rats, intravenous hexamethonium injection induced a blood pressure reduction 240% of that in control rats, and significantly increased the levels of superoxide anion and NAD(P)H oxidase activity in the hypothalamus. Intracerebroventricular microinjection of tempol also resulted in more significant changes of MAP, HR and RSNA in DOCA-salt rats than in the control group (P<0.01).
Sympathoexcitation due to increased NAD(P)H oxidase-derived ROS levels in the hypothalamus may mediate arterial pressure elevation in DOCA-salt hypertensive rats.
研究脑内活性氧是否介导去氧皮质酮盐（DOCA-盐）高血压大鼠的交感神经兴奋和动脉血压升高。
雄性SD大鼠行单侧肾切除术后皮下注射DOCA，并饮用1%氯化钠溶液4周，建立DOCA-盐高血压模型。在轻度麻醉下记录大鼠的基线平均动脉压（MAP）、心率（HR）和肾交感神经活动（RSNA），并观察静脉注射六甲铵后MAP的变化。评估MAP、HR和RSNA对脑室内注射tempol（10 μl中含20 μmol/L）的反应；采用酶联免疫吸附测定法测定血浆去甲肾上腺素（NE）水平，使用化学发光分析法检测下丘脑活性氧水平和NAD(P)H氧化酶活性。
与对照组相比，DOCA-盐大鼠的MAP和血浆NE水平显著升高（P<0.01）。在DOCA-盐高血压大鼠中，静脉注射六甲铵引起的血压下降幅度是对照组大鼠的240%，并显著增加下丘脑超氧阴离子水平和NAD(P)H氧化酶活性。脑室内微量注射tempol也导致DOCA-盐大鼠的MAP、HR和RSNA变化比对照组更显著（P<0.01）。
下丘脑内NAD(P)H氧化酶衍生的活性氧水平升高所致的交感神经兴奋可能介导DOCA-盐高血压大鼠的动脉血压升高。
