Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Neuroscience. 2012 Oct 25;223:388-98. doi: 10.1016/j.neuroscience.2012.07.048. Epub 2012 Jul 31.
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 α-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.
血管紧张素 (Ang)-(1-7) 和血管紧张素 II 在延髓头端腹外侧区 (RVLM) 均增加肾交感神经活动 (RSNA) 和平均动脉压 (MAP)，并增强心脏交感传入反射 (CSAR)。RVLM 中的 NAD(P)H 氧化酶衍生的超氧阴离子介导血管紧张素 II 对 CSAR 和交感活动的作用。然而，超氧阴离子是否介导 RVLM 中 Ang-(1-7) 的作用尚不清楚。本研究旨在确定超氧阴离子是否介导 RVLM 中 Ang-(1-7) 的作用，包括增加 RSNA 和 MAP，并增强 CSAR，并确定 NAD(P)H 氧化酶是否是大鼠中超氧阴离子的主要来源。RSNA 和 MAP 在去窦弓神经和颈迷走神经切断的乌拉坦和α-氯醛糖麻醉大鼠中记录。心脏交感传入反射通过心外膜应用辣椒素评估 RSNA 和 MAP 反应。RVLM 双侧微注射超氧阴离子清除剂 Tempo 或 Tiron，或 NAD(P)H 氧化酶抑制剂 Apocynin，抑制 Ang-(1-7)在 RVLM 中的作用，而超氧化物歧化酶 (SOD) 抑制剂二乙基二硫代氨基甲酸盐 (DETC) 增强 Ang-(1-7)的作用。Ang-(1-7)增加，但 Mas 受体拮抗剂 D-丙氨酸-Ang-(1-7) (A-779) 降低 RVLM 中的 NAD(P)H 氧化酶活性和超氧阴离子水平。RVLM 预先用 Apocynin 或 A-779 处理可消除 Ang-(1-7) 诱导的 NAD(P)H 氧化酶活性和超氧阴离子水平的增加，但不能消除 AT(1) 受体拮抗剂 Losartan。心外膜应用辣椒素增加 NAD(P)H 氧化酶活性和超氧阴离子水平；该作用被 A-779 抑制，被 Ang-(1-7) 增强。这些结果表明，超氧阴离子参与调节 RVLM 中 Ang-(1-7) 和 Mas 受体的作用：增加 RSNA 和 MAP，并增强 CSAR。NAD(P)H 氧化酶的酶是调节 RVLM 中 Ang-(1-7) 作用的超氧阴离子的主要来源。
