Over-expression of copper/zinc superoxide dismutase in the median preoptic nucleus attenuates chronic angiotensin II-induced hypertension in the rat.
Over-expression of copper/zinc superoxide dismutase in the median preoptic nucleus attenuates chronic angiotensin II-induced hypertension in the rat.
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DOI：
10.3390/ijms151222203
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发表时间：
2014-12-02
影响因子：
5.6
通讯作者：
Zimmerman MC
中科院分区：
文献类型：
--
作者：
Collister JP;Bellrichard M;Drebes D;Nahey D;Tian J;Zimmerman MC
大脑通过室周器官（例如穹窿下器官（SFO））感测血管紧张素II（AngII）的循环水平，并且被认为通过这种神经激素通信相应地调节交感神经系统输出。然而，这些通信中涉及的细胞信号传导机制仍有待充分理解。先前对SFO或下游正中视前核（MnPO）的损伤研究显示慢性AngII的高血压效应减弱，但未对所涉及的细胞内信号通路提供明确解释。另外的研究报道，在SFO中过表达铜/锌超氧化物歧化酶（CuZnSOD），一种细胞内超氧化物（O2·−）清除酶，可减轻慢性AngII诱导的高血压。在此，我们检验了MnPO中O2·−的过量产生是慢性AngII长期高血压效应的潜在机制的假设。将编码人CuZnSOD的腺病毒载体（AdCuZnSOD）或对照载体（AdEmpty）直接注射到植入主动脉遥测发射器的大鼠的MnPO中以记录动脉压。在盐水输注的3天对照期之后，大鼠静脉内输注AngII（10 ng/kg/min）10天。在MnPO中过表达CuZnSOD的大鼠（n = 7）在AngII输注10天后血压仅升高6 ± 2 mmHg，而AdEmpty感染的大鼠（n = 9）血压升高21 ± 4 mmHg。这些结果支持了MnPO中O2·−的产生有助于慢性AngII依赖性高血压的发展的假设。
The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·−) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·− in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2·− in the MnPO contributes to the development of chronic AngII-dependent hypertension.
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影响因子：
2.1
作者：
FERGUSON, AV;WALL, KM
通讯作者：
WALL, KM
影响因子：
2.9
作者：
GUTMAN, MB;CIRIELLO, J;MOGENSON, GJ
通讯作者：
MOGENSON, GJ
影响因子：
4.1
作者：
MANGIAPANE, ML;THRASHER, TN;GANONG, WF
通讯作者：
GANONG, WF
DOI：
10.1111/j.1749-6632.1993.tb55545.x
发表时间：
1993-07-22
影响因子：
5.2
作者：
ZARDETTOSMITH, AM;THUNHORST, RL;JOHNSON, AK
通讯作者：
JOHNSON, AK
影响因子：
4.1
作者：
MANGIAPANE, ML;SIMPSON, JB
通讯作者：
SIMPSON, JB