Angiotensin II-Induced Hypertension Is Attenuated by Overexpressing Copper/Zinc Superoxide Dismutase in the Brain Organum Vasculosum of the Lamina Terminalis.
Angiotensin II-Induced Hypertension Is Attenuated by Overexpressing Copper/Zinc Superoxide Dismutase in the Brain Organum Vasculosum of the Lamina Terminalis.
复制标题
终层脑器官血管中铜/锌超氧化物歧化酶的过度表达可减轻血管紧张素 II 诱发的高血压。
DOI：
10.1155/2016/3959087
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发表时间：
2016
影响因子：
--
通讯作者：
Zimmerman,MatthewC
中科院分区：
文献类型：
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作者：
Collister,JohnP;Taylor-Smith,Heather;Drebes,Donna;Nahey,David;Tian,Jun;Zimmerman,MatthewC
血管紧张素II（AngII）可通过室周器官（CVO）（包括穹窿下器官（SFO）和终板血管器（OVLT））进入脑以调节血压。先前的研究已经证明了SFO和OVLT在慢性AngII高血压反应中的作用，但尚不清楚哪些细胞内信号通路参与了这种反应。铜/锌超氧化物歧化酶（CuZnSOD）在SFO中的过表达已被证明可以减弱AngII的慢性高血压效应。目前，我们验证了OVLT中超氧化物（）水平升高有助于AngII的高血压效应的假设。为了促进超氧化物歧化酶的过表达，将编码人CuZnSOD的腺病毒载体或对照腺病毒（AdEmpty）直接注射到大鼠的OVLT中。对照盐水输注3天后，大鼠静脉输注AngII（10 ng/kg/min）10天。AdEmpty大鼠（n= 6）的血压升高33 ± 8 mmHg，而OVLT中过表达CuZnSOD的大鼠（n= 8）在AngII输注10天后显示血压仅升高18 ± 5 mmHg。这些结果支持OVLT中过量产生的在慢性AngII依赖性高血压的发展中起重要作用的假设。
Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide () in the OVLT contribute to the hypertensive effects of AngII. To facilitate overexpression of superoxide dismutase, adenoviral vectors encoding human CuZnSOD or control adenovirus (AdEmpty) were injected directly into the OVLT of rats. Following 3 days of control saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Blood pressure increased 33 ± 8 mmHg in AdEmpty rats (n= 6), while rats overexpressing CuZnSOD (n= 8) in the OVLT demonstrated a blood pressure increase of only 18 ± 5 mmHg after 10 days of AngII infusion. These results support the hypothesis that overproduction ofin the OVLT plays an important role in the development of chronic AngII‐dependent hypertension.