SUPEROXIDE ANIONS MODULATE THE EFFECTS OF ANGIOTENSIN-(1-7) IN THE ROSTRAL VENTROLATERAL MEDULLA ON CARDIAC SYMPATHETIC AFFERENT REFLEX AND SYMPATHETIC ACTIVITY IN RATS
SUPEROXIDE ANIONS MODULATE THE EFFECTS OF ANGIOTENSIN-(1-7) IN THE ROSTRAL VENTROLATERAL MEDULLA ON CARDIAC SYMPATHETIC AFFERENT REFLEX AND SYMPATHETIC ACTIVITY IN RATS
复制标题
超氧阴离子调节大鼠头端腹外侧延髓血管紧张素-(1-7)对心脏交感神经反射和交感神经活动的影响
DOI：
10.1016/j.neuroscience.2012.07.048
复制
发表时间：
2012-10-25
期刊：
影响因子：
3.3
通讯作者：
Han, Y.
中科院分区：
文献类型：
--
作者：
Li, P.;Zhang, F.;Han, Y.
延髓头端腹外侧区（RVLM）的血管紧张素（Ang）-（1-7）和血管紧张素Ⅱ（Ang Ⅱ）均能增加肾交感神经活动（RSNA）和平均动脉压（MAP），增强心交感传入反射（CSAR）。RVLM中NAD（P）H氧化酶衍生的超氧阴离子介导了Ang II对CSAR和交感神经活性的影响。然而，超氧阴离子是否介导Ang-（1-7）在RVLM中的作用尚不清楚。本研究旨在探讨超氧阴离子是否介导Ang-（1-7）在大鼠RVLM中的作用，包括增加RSNA和MAP以及增强CSAR，并确定NAD（P）H氧化酶是否是超氧阴离子的主要来源。用乌拉坦和α-氯醛糖麻醉，记录去交感神经和颈迷走神经大鼠的RSNA和MAP。通过RSNA和MAP对心外膜应用辣椒素的反应来评估CSAR。双侧RVLM微量注射超氧阴离子清除剂tempol或tiron或NAD（P）H氧化酶抑制剂apocynin可抑制Ang-（1-7）在RVLM的作用，而超氧化物歧化酶（SOD）抑制剂二乙基二硫代氨基甲酸（DETC）可增强Ang-（1-7）的作用。Ang-（1-7）可增加RVLM的NAD（P）H氧化酶活性和超氧阴离子水平，而Mas受体拮抗剂D-丙氨酸-Ang-（1-7）（A-779）可降低RVLM的NAD（P）H氧化酶活性和超氧阴离子水平。用夹竹桃素或A-779预处理RVLM可消除Ang-（1-7）引起的NAD（P）H氧化酶活性和超氧阴离子水平的升高，但AT（1）受体拮抗剂氯沙坦不能消除。心外膜应用辣椒素可增加NAD（P）H氧化酶活性和超氧阴离子水平，这种作用可被A-779抑制，被Ang-（1-7）增强。以上结果表明，超氧阴离子参与了RVLM中Ang-（1-7）和Mas受体的调节作用，使RSNA和MAP增加，CSAR增强。NAD（P）H氧化酶是调节RVLM中Ang-（1-7）作用的超氧阴离子的主要来源。(c)2012年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Both angiotensin (Ang)-(1-7) and Ang II in the rostral ventrolateral medulla (RVLM) increase renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) and enhance the cardiac sympathetic afferent reflex (CSAR). NAD(P)H oxidase-derived superoxide anions in the RVLM mediate the effects of Ang II on CSAR and sympathetic activity. However, whether the superoxide anions mediate the effects of Ang-(1-7) in RVLM is still unclear. This study was designed to determine whether superoxide anions mediate the effects of Ang-(1-7) in the RVLM, including increasing the RSNA and MAP and enhancing the CSAR, and to determine whether NAD(P)H oxidase is the major origin of the superoxide anions in rats. RSNA and MAP were recorded in sinoaortic-denervated and cervical-vagotomized rats with urethane and alpha-chloralose anesthesia. The CSAR was evaluated by the RSNA and MAP responses to the epicardial application of capsaicin. Bilateral RVLM microinjection of the superoxide anion scavengers tempol or tiron, or the NAD(P)H oxidase inhibitor apocynin inhibited the effects of Ang-(1-7) in RVLM, while the superoxide dismutase (SOD) inhibitor diethyldithiocarbamic acid (DETC) potentiated the effects of Ang-(1-7). Ang-(1-7) increased but Mas receptor antagonist D-Alanine-Ang-(1-7) (A-779) decreased the NAD(P)H oxidase activity and superoxide anion level in the RVLM. The Ang-(1-7)-induced increases in NAD(P)H oxidase activity and superoxide anion level were abolished by pre-treating the RVLM with apocynin or A-779 but not the AT(1) receptor antagonist losartan. The epicardial application of capsaicin increased NAD(P)H oxidase activity and superoxide anion level; the effect was inhibited by A-779 and enhanced by Ang-(1-7). These results indicate that superoxide anions are involved in modulating the effects of Ang-(1-7) and Mas receptor in the RVLM: increasing the RSNA and MAP and enhancing the CSAR. The enzyme of NAD(P)H oxidase is a major source of the superoxide anions that modulate the effects of Ang-(1-7) in the RVLM. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.