Role of reactive oxygen species within the vasomotor center of the brain in hypertension

高血压患者的氧化应激增加。本研究的目的是确定卒中易感自发性高血压大鼠(SHRSP)脑干头端腹外侧延髓(RVLM)血管运动中枢所在的活性氧(ROS)是否增加，如果是，确定ROS增加是否参与SHRSP高血压的神经机制。我们测定了SHRSP大鼠RVLM的ROS水平，并与Wistar-京都大鼠(WKY)的ROS水平进行了比较。SHRSP组与WKY组比较，硫代巴比妥酸反应物质增多。用电子自旋共振(ESR)波谱测定了ROS。SHRSP的RVLM的ESR信号衰减率较WKY显著增加，这种增加可被羟基自由基清除剂二甲基硫脲所消除。在去铁胺、过氧化氢酶和TIron的存在下，增加的ESR信号衰减也有相同程度的减少，表明羟基自由基来自超氧阴离子和过氧化氢。此外，SHRSP组RVLM中总超氧化物歧化酶(SOD)活性降低血压，而WKY组无此作用；SHRSP组RVLM中MnSOD过表达可降低血压，抑制交感神经活动。这些结果提示，SHRSP时，RVLM中产生羟基自由基的超氧阴离子增多，参与了SHRSP高血压的神经机制。我们还研究了RVLM中诱导型一氧化氮合酶(INOS)在控制血压和交感神经活动中的作用。我们发现，iNOS在RVLM中的过度表达通过激活交感神经系统来增加血压，而交感神经系统是通过增加氧化应激来调节的。

Oxidative stress increases in hypertension. The aim of this study was to determine whether reactive oxygen species(ROS) are increased in the rostral ventrolateral medulla(RVLM) in the brainstem, where the vasomotor center is located, in stroke-prone spontaneously hypertensive rats(SHRSP), and, if so, to determine whether the increased ROS contribute to neural mechanisms of hypertension in SHRSP. We measured ROS levels in the RVLM of SHRSP and compared them with those in Wistar-Kyoto rats(WKY). Thiobarbituric acid-reactive substances were increased in SHRSP compared with WKY. ROS were also measured by electron spin resonance(ESR) spectroscopy. The ESR signal decay rate in the RVLM of SHRSP was significantly increased compared with that in WKY, and this increase was abolished by dimethylthiourea (a hydroxyl radical scavenger). The increased ESR signal decay was reduced to the same extent in the presence of desferrioxamine, catalase, and Tiron, indicating that hydroxyl radicals are derived from superoxide anions and hydrogen peroxide. In addition, total superoxide dismutase(SOD) activity in the RVLM decreased blood pressure in SHRSP but not in WKY, and MnSOD overexpression in the RVLM of SHRSP decreased blood pressure and inhibited sympathetic nerve activity. These results suggest that superoxide anions in the RVLM, which generate hydroxyl radicals, are increased in SHRSP and contribute to the neural mechanisms of hypertension in SHRSP. We also examined the role of inducible nitric oxide synthase(iNOS) in the RVLM in the control of blood pressure and sympathetic nerve activity. We fond that overexpression of iNOS in the RVLM increases blood pressure via activation of the sympathetic nervous system, which is mediated by an increase in oxidative stress.