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

高血压患者氧化应激增加。本研究旨在确定卒中易发自发性高血压大鼠（SHRSP）血管舒缩中枢所在的脑干吻侧腹外侧髓质（RVLM）中活性氧（ROS）是否增加，如果增加，则确定ROS的增加是否与SHRSP中高血压的神经机制有关。我们测量了SHRSP RVLM中的ROS水平，并与Wistar-Kyoto大鼠（WKY）进行了比较。与WKY相比，SHRSP中硫代巴比妥酸活性物质增加。用电子自旋共振（ESR）光谱法测定活性氧。与WKY相比，SHRSP的RVLM中ESR信号衰减率显著增加，而这种增加被二甲基硫脲（一种羟基自由基清除剂）所消除。在去铁胺、过氧化氢酶和铁的存在下，增加的ESR信号衰减也有相同程度的减少，这表明羟基自由基来源于超氧阴离子和过氧化氢。此外，RVLM中总超氧化物歧化酶（SOD）活性降低了SHRSP的血压，但在WKY中没有，SHRSP RVLM中MnSOD过表达降低了血压，抑制了交感神经活动。这些结果表明，在SHRSP中，RVLM中产生羟基自由基的超氧阴离子增加，并参与了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，RVLM中iNOS的过度表达通过激活交感神经系统而增加血压，这是由氧化应激增加介导的。

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.