Renin-angiotensin system acting on reactive oxygen species in paraventricular nucleus induces sympathetic activation via AT1R/PKCγ/Rac1 pathway in salt-induced hypertension.
Renin-angiotensin system acting on reactive oxygen species in paraventricular nucleus induces sympathetic activation via AT1R/PKCγ/Rac1 pathway in salt-induced hypertension.
复制标题
盐诱发高血压中肾素-血管紧张素系统作用于室旁核活性氧，通过 AT1R/PKC gamma/Rac1 途径诱导交感神经激活
DOI：
10.1038/srep43107
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发表时间：
2017-03-24
影响因子：
4.6
通讯作者：
Kang YM
中科院分区：
文献类型：
--
作者：
Su Q;Huo CJ;Li HB;Liu KL;Li X;Yang Q;Song XA;Chen WS;Cui W;Zhu GQ;Shi XL;Liu JJ;Kang YM
在高血压的发生发展过程中，脑内的肾素-血管紧张素系统（RAS）可调节室旁核（PVN）内的氧化应激。本研究旨在探讨RAS在盐性高血压中对活性氧（ROS）的确切作用机制。雄性Wistar大鼠给予高盐饮食（HS，8.0%NaCl）8周诱导高血压。PVN内注射AT 1 R拮抗剂氯沙坦（LOS，10 μg/h）或微量注射PKCγ siRNA，每天1次，共2周。高盐组PVN中AT 1 R、PKCγ、Rac 1活性、超氧化物歧化酶（Cu/Zn-SOD）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）活性均显著高于对照组，而MDA和SOD活性显著高于对照组。PVN灌注LOS不仅能降低PVN的AT 1 R、PKCγ、Rac 1活性、超氧化物歧化酶（SOD）水平，降低动脉血压，而且能增强PVN的抗氧化能力。室旁核注射PKCγ siRNA对LOS的影响与高血压反应相同，但对室旁核AT 1 R水平无影响。这些结果首次证实了盐性高血压中RAS调控室旁核ROS的确切信号通路是通过AT 1 R/PKCγ/Rac 1。
Brain renin-angiotensin system (RAS) could regulate oxidative stress in the paraventricular nucleus (PVN) in the development of hypertension. This study was designed to explore the precise mechanisms of RAS acting on reactive oxygen species (ROS) in salt-induced hypertension. Male Wistar rats were administered with a high-salt diet (HS, 8.0% NaCl) for 8 weeks to induced hypertension. Those rats were received PVN infusion of AT1R antagonist losartan (LOS, 10 μg/h) or microinjection of small interfering RNAs for protein kinase C γ (PKCγ siRNA) once a day for 2 weeks. High salt intake resulted in higher levels of AT1R, PKCγ, Rac1 activity, superoxide and malondialdehyde (MDA) activity, but lower levels of copper/zinc superoxide dismutase (Cu/Zn-SOD), superoxide dismutase (SOD) and glutathione (GSH) in PVN than control animals. PVN infusion of LOS not only attenuated the PVN levels of AT1R, PKCγ, Rac1 activity, superoxide and decreased the arterial pressure, but also increased the PVN antioxidant capacity in hypertension. PVN microinjection of PKCγ siRNA had the same effect on LOS above responses to hypertension but no effect on PVN level of AT1R. These results, for the first time, identified that the precise signaling pathway of RAS regulating ROS in PVN is via AT1R/PKCγ/Rac1 in salt-induced hypertension.