Role of angiotensin-(1-7) and Mas-R-nNOS pathways in amplified neuronal activity of dorsolateral periaqueductal gray after chronic heart failure.
Role of angiotensin-(1-7) and Mas-R-nNOS pathways in amplified neuronal activity of dorsolateral periaqueductal gray after chronic heart failure.
复制标题
血管紧张素-(1-7) 和 Mas-R-nNOS 通路在慢性心力衰竭后背外侧导水管周围灰质神经元活动增强中的作用。
DOI：
10.1016/j.neulet.2014.01.025
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发表时间：
2014
影响因子：
2.5
通讯作者：
Li,Jianhua
中科院分区：
文献类型：
--
作者：
Xing,Jihong;Lu,Jian;Li,Jianhua
中脑导水管周围灰质（PAG）是一个由交感神经系统驱动的整合性神经中枢，参与包括心血管活动在内的多种生理功能的调节。具体地，背外侧PAG（dl-PAG）的激活导致交感神经活动和动脉血压的增加。本课题组近年来的研究表明，血管紧张素-（1-7）[Ang-（1-7）]通过Mas-R [Ang-（1-7）受体]和神经元NO依赖性信号通路（Mas-R-nNOS）抑制dl-PAG的神经元活性。由于慢性心力衰竭（HF）时交感神经活动增强，本研究测定（1）对照组和HF组大鼠dl-PAG内Ang-（1-7）和Mas-R-nNOS的表达水平以及（2）Ang-（1-7）在两组dl-PAG神经元活动调节中的作用。结果表明，慢性HF可降低Ang-（1-7）水平，减弱Mas-R-nNOS通路。此外，我们还证实了HF大鼠dl-PAG神经元的放电频率（5.52 ± 0.52Hz，n= 21，P< 0.05vs.control）与对照组比较，差异有统计学意义（4.03 ± 0.39 Hz，n= 28），Ang-（1-7）对dl-PAG神经元电活动的抑制作用在HF时显著降低（51 ± 6%，P <0.05vs.）与对照组（72 ± 8%）比较。我们的研究结果表明，Ang-（1-7）对dl-PAG神经元的抑制作用在HF中受损，可能是由于Mas-R-nNOS信号通路减弱。
The midbrain periaqueductal gray (PAG) is an integrative neural site in regulating several physiological functions including cardiovascular activities driven by sympathetic nervous system. Specifically, activation of the dorsolateral PAG (dl-PAG) leads to increases in sympathetic nervous activity and arterial blood pressure. Our recent studies demonstrated that angiotensin-(1–7) [Ang-(1–7)] plays an inhibitory role in neuronal activity of the dl-PAGviaa Mas-R [Ang-(1–7) receptor] and neuronal NO dependent signaling pathway (Mas-R-nNOS). Because sympathetic nervous activity is augmented in chronic heart failure (HF), the present study was to determine (1) the levels of Ang-(1–7) and Mas-R-nNOS expression within the dl-PAG of control rats and rats with HF and (2) the role for Ang-(1–7) in modulating activity of dl-PAG neurons in both groups. Results showed that chronic HF decreased the levels of Ang-(1–7) and attenuated Mas-R-nNOS pathways. Also, we demonstrated that the discharge rates of dl-PAG neurons of HF rats (5.52 ± 0.52 Hz,n= 21,P< 0.05vs.control) were augmented as compared with control rats (4.03 ± 0.39 Hz,n= 28) and an inhibitory role played by Ang-(1–7) in neuronal activity of the dl-PAG was significantly decreased in HF (51 ± 6%,P< 0.05vs.control) as compared with controls (72 ± 8%). Our findings suggest that the inhibitory effects of Ang-(1–7) on dl-PAG neurons are impaired in HF, likely due to attenuated Mas-R-nNOS signaling pathways.