Reactive oxygen species stimulate central and peripheral sympathetic nervous system activity
Reactive oxygen species stimulate central and peripheral sympathetic nervous system activity
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DOI：
10.1152/ajpheart.00619.2003
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发表时间：
2004-08-01
影响因子：
4.8
通讯作者：
Chiu, J
中科院分区：
文献类型：
--
作者：
Campese, VM;Ye, SH;Chiu, J
近年来的研究表明，活性氧（ROS）参与了高血压的发病机制和交感神经系统（SNS）的激活。由于一氧化氮（NO）对中枢SNS活动具有紧张性抑制作用，因此ROS产生的增加可增强NO的失活并导致SNS的激活。为了验证ROS可能调节SNS活性的假设，我们通过静脉（250 www.example.com（-1）.min（-1））或侧脑室输注Tempol（4-羟基-2，2，6，6-四甲基哌啶氧基），一种超氧化物歧化酶模拟物或载体mug.kg（50 μ g. kg体重（-1）.min（-1）），我们测定了对血压（BP）的影响，通过微透析技术测定了下丘脑后部（PH）的去甲肾上腺素（NE）分泌，采用直接显微神经造影法测定肾交感神经活性（RSNA），RT-PCR法测定PH、室旁核（PVN）和蓝斑（LC）中神经元型一氧化氮合酶（nNOS）-mRNA的丰度，以及PH前收集的透析液中硝酸盐/亚硝酸盐（NOx）的分泌。无论是静脉注射还是脑室内注射，Tempol都能降低血压。脑室注射Tempol可减少PH和RSNA前的NE分泌，而静脉注射Tempol可增加PH和RSNA前的NE分泌。静脉Tempol对SNS活动的影响被窦弓去神经所减弱或消除。Tempol增加nNOS在PH，PVN和LC的丰度时，脑室内灌注，但它减少nNOS的丰度时，静脉内灌注。当给予intracerebroventricularly，Tempol也减少了从PH收集的透析液中的NOx的浓度。用N-ω-硝基-L-精氨酸甲酯预处理并没有取消脑内Tempol对BP的影响。心率NE分泌的PH，和RSNA表明，Tempol对SNS活动的影响可能是部分依赖和部分独立的NO。总之，这些研究支持的概念，ROS可能会通过激活的SNS提高BP。这种激活可能是介导的部分下调nNOS和NO的生产，部分由独立的NO的机制。脑室内和静脉输注Tempol的结果之间的差异可以最好地解释SNS活动的直接抑制作用时，给予脑内。相比之下，Ternpol可以发挥直接的血管扩张外周循环和反射激活的SNS静脉注射时。
Recent studies have implicated reactive oxygen species (ROS) in the pathogenesis of hypertension and activation of the sympathetic nervous system (SNS). Because nitric oxide (NO) exerts a tonic inhibition of central SNS activity, increased production of ROS could enhance inactivation of NO and result in activation of the SNS. To test the hypothesis that ROS may modulate SNS activity, we infused Tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl), a superoxide dismutase mimetic, or vehicle either intravenously (250 mug.kg(-1).min(-1)) or in the lateral ventricle (50 mug.kg body wt(-1).min(-1)), and we determined the effects on blood pressure (BP), norepinephrine (NE) secretion from the posterior hypothalamus (PH) measured by the microdialysis technique, renal sympathetic nerve activity (RSNA) measured by direct microneurography, the abundance of neuronal NO synthase (nNOS)-mRNA in the PH, paraventricular nuclei (PVN), and locus coeruleus (LC) measured by RT-PCR, and the secretion of nitrate/nitrite (NOx) in the dialysate collected front the PH of Sprague-Dawley rats. Tempol reduced BP whether infused intravenously or intracerebroventricularly. Tempol reduced NE secretion front the PH and RSNA when infused intracerebroventricularly but raised NE secretion from the PH and RSNA when infused intravenously. The effects of intravenous Tempol on SNS activity were blunted or abolished by sinoaortic denervation. Tempol increased the abundance of nNOS in the PH, PVN, and LC when infused intracerebroventricularly, but it decreased the abundance of nNOS when infused intravenously. When given intracerebroventricularly, Tempol also reduced the concentration of NOx in the dialysate collected from the PH. Pretreatment with N-omega-nitro-L-arginine methyl ester did not abolish the effects of intracerebral Tempol on BP. heart rate. NE secretion from the PH, and RSNA suggesting that the effects of Tempol on SNS activity may be in part dependent and in part independent of NO. In all, these Studies Support the notion that ROS may raise BP via activation of the SNS. This activation may be mediated in part by downregulation of nNOS and NO production, in part by mechanisms independent of NO. The discrepancy in results between intracerebroventricular and intravenous infusion of Tempol can be best explained by direct inhibitory actions on SNS activity when given intracerebral. By contrast, Ternpol may exert direct vasodilation of the peripheral circulation and reflex activation of the SNS when given intravenously.