Central Tempol alters basal sympathetic nerve discharge and attenuates sympathetic excitation to central ANG II
Central Tempol alters basal sympathetic nerve discharge and attenuates sympathetic excitation to central ANG II
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DOI：
10.1152/ajpheart.00030.2004
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发表时间：
2004-12-01
影响因子：
4.8
通讯作者：
Kenney, MJ
中科院分区：
文献类型：
--
作者：
Lu, N;Helwig, BG;Kenney, MJ
在本研究中，我们建立了4-羟基-2,2,6,6-四甲基哌啶1-氧基（Tempol，一种超氧化物歧化酶模拟物）的中枢给药与肾交感神经放电（SND）水平之间的剂量-反应关系，并测试了脑室内（icv）Tempol预处理会减弱由icv ANG II给药产生的中枢介导的SND变化的假设。使用尿烷-氯醛糖麻醉、压力感受器去神经、血压正常的大鼠。我们发现 icv Tempol 给药产生剂量依赖性交感神经抑制、低血压和心动过缓反应。给予icv ANG II (150 ng/kg)后，平均动脉压和SND值显着增加，而在用Tempol (75 mumol/kg)或氯沙坦进行icv预处理后，这些反应被消除。与接受 Tempol 和 ANG II 治疗的大鼠相比，接受 ANG II 治疗的大鼠脑超氧化物水平往往更高。 Tempol 预处理并不能阻止急性热应激引起的 SND 水平升高，这表明 Tempol 在减少交感神经兴奋方面具有特异性作用。这些结果表明，icv Tempol 给药以剂量依赖性方式影响中枢交感神经回路，并减弱 SND 对中枢 ANG II 输注的反应。
In the present study, we established dose-response relationships between central administration of 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol, a superoxide dismutase mimetic) and the level of renal sympathetic nerve discharge (SND) and tested the hypothesis that intracerebroventricular (icv) Tempol pretreatment would attenuate centrally mediated changes in SND produced by icv ANG II administration. Urethane-chloralose-anesthetized, baroreceptor-denervated, normotensive rats were used. We found that icv Tempol administration produced dose-dependent sympathoinhibitory, hypotensive, and bradycardic responses. Mean arterial pressure and SND values were significantly increased after icv ANG II (150 ng/kg) administration, and these responses were abrogated after icv pretreatment with Tempol (75 mumol/kg) or losartan. Brain superoxide levels tended to be higher in ANG II-treated rats compared with rats treated with Tempol and ANG II. Tempol pretreatment did not prevent increases in SND level that were produced by acute heat stress, which indicates specificity in the effect of Tempol in reducing sympathoexcitation. These results demonstrate that icv Tempol administration influences central sympathetic neural circuits in a dose-dependent manner and attenuates SND responses to central ANG II infusion.