Activation of central angiotensin type 2 receptors suppresses norepinephrine excretion and blood pressure in conscious rats.
Activation of central angiotensin type 2 receptors suppresses norepinephrine excretion and blood pressure in conscious rats.
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DOI：
10.1038/ajh.2011.33
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发表时间：
2011-06
影响因子：
3.2
通讯作者：
Gao, Lie
中科院分区：
文献类型：
--
作者：
Gao, Juan;Zhang, Hao;Le, Khang D.;Chao, Jie;Gao, Lie
关键词：
我们以前的文献表明，中枢血管紧张素2型受体（AT2R）负调节交感神经流出和动脉血压（BP）。在本研究中，我们测定了第一种选择性非肽AT2R激动剂化合物21 （C21）在脑室内（icv）输注对大鼠去甲肾上腺素（NE）排泄和血压的影响。微渗透泵静脉滴注C21 7 d。尿NE浓度测定采用去甲肾上腺素酶免疫测定试剂盒。用无线电遥测法记录血压。7 d后处死大鼠，用Western Blot方法对脑内3个交感神经相关区域和大脑皮层进行微穿孔检测nNOS蛋白表达。此外，采用全细胞膜片钳法测定C21对神经元钾电流（IKv）的影响。(1) icv处理C21显著降低夜间尿NE浓度和量，但对日间尿NE无影响。(2) C21处理大鼠血压有轻微但显著的降低。(3) C21对NE排泄和血压的影响被AT2R拮抗剂PD123319和一氧化氮合酶（NOS）抑制剂L-NAME所消除。(4) C21处理显著上调PVN和RVLM中nNOS的表达，而NTS和大脑皮层中nNOS的表达不上调。(5)在CATH。a神经元中，C21处理显著增加IKv， PD123319和L-NAME完全消除IKv。这些结果表明，C21对交感神经流出的中枢抑制作用可能通过nNOS依赖机制，并可能通过促进神经元钾通道介导。
We have previously documented that central Angiotensin type 2 receptors (AT2R) negatively modulate sympathetic outflow and arterial blood pressure (BP). In the current study, we determined the effects of intracerebroventricular (icv) infusion of Compound 21 (C21), the first selective non-peptide AT2R agonist, on norepinephrine (NE) excretion and BP in rats. C21 was icv infused by a Micro-osmotic pump for 7 days. Urinary NE concentration was measured using the Norepinephrine Enzyme Immunoassay kit. BP was recorded by radiotelemetry. After 7 days, the rats were euthanized and three sympathetic relevant brain regions and cerebral cortex were micro-punched to measure nNOS protein expression by Western Blot. In addition, the influence of C21 on neuronal potassium current (IKv) was determined by whole cell patch-clamp in a neuron cell-line, CATH.a. (1) icv treatment of C21 significantly decreased NE concentration and amount in nighttime urine but had no effect in daytime urine. (2) C21 treated rats exhibited a slight but significant decrease in BP. (3) The effects of C21 on NE excretion and BP were abolished by AT2R antagonist, PD123319, and nitric oxide synthase (NOS) inhibitor, L-NAME. (4) C21 treatment significantly up regulated nNOS expression in the PVN and RVLM, but not in the NTS and cerebral cortex. (5) In CATH.a neurons, C21 treatment significantly increased IKv, which was completely abolished by PD123319 and L-NAME. These results demonstrate a central inhibitory influence of C21 on sympathetic outflow via a nNOS dependent mechanism, which might be mediated by facilitating neuronal potassium channel.
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影响因子：
7.3
作者：
Wan, YQ;Wallinder, C;Alterman, M
通讯作者：
Alterman, M
影响因子：
--
作者：
KANG, J;SUMNERS, C;POSNER, P
通讯作者：
POSNER, P
DOI：
10.1152/ajpheart.00030.2004
发表时间：
2004-12-01
影响因子：
4.8
作者：
Lu, N;Helwig, BG;Kenney, MJ
通讯作者：
Kenney, MJ
影响因子：
7.3
作者：
Bosnyak, S.;Welungoda, I. K.;Jones, E. S.
通讯作者：
Jones, E. S.
影响因子：
2.5
作者：
Han, NLR;Ye, JS;Sheu, FS
通讯作者：
Sheu, FS