脑内活性氧抑制对醋酸去氧皮质酮-盐型高血压大鼠交感神经活动的影响

Effect of inhibiting brain reactive oxygen species on sympathetic nerve activity in DOCA-salt hypertensive rats

目的探讨脑内活性氧是否介导醋酸去氧皮质酮(DOCA)-盐型高血压大鼠的交感神经活动增强效应。方法雄性SD大鼠,行左肾切除术后皮下注射DOCA,并饮用1%氯化钠溶液4周,建立DOCA-盐型高血压模型。轻度麻醉状态下,记录大鼠平均动脉压(MAP)、心率(HR)和肾交感神经活动(RSNA);记录基础值后,静脉注射六烃季胺,观察MAP的变化;侧脑室注射tempol(20μmol/L,10μl)或对照液,观察MAP、HR和RSNA的变化。酶联免疫法(ELISA)分析血浆去甲肾上腺素(NE)水平;化学发光法检测下丘脑超氧阴离子水平和NAD(P)H氧化酶活性。结果 DOCA-盐型大鼠的MAP和血浆NE水平较对照组均显著增加(P<0.01);静脉注射神经节阻滞剂六烃季胺,在DOCA-盐型大鼠引起的血压降低是对照大鼠的240%;DOCA-盐型大鼠的下丘脑超氧阴离子水平和NAD(P)H氧化酶活性显著增加(P<0.01);侧脑室微注射tempol在DOCA-盐型大鼠的MAP、HR和RSNA降低与对照组存在显著差异(P<0.01)。结论 DOCA-盐型高血压大鼠可能通过增加下丘脑内NAD(P)H氧化酶来源的活性氧水平,提高交感神经活性,参与高血压的形成和进展。

Objective To investigate whether brain reactive oxygen species mediate sympathoexcitation and arterial pressure elevation in DOCA- salt hypertensive rats. Methods 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.Results 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 reduction240% 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）. Conclusion Sympathoexcitation due to increased NAD（P）H oxidase-derived ROS levels in the hypothalamus may mediate arterial pressure elevation in DOCA-salt hypertensive rats.