Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension
Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension
复制标题
脑核因子-κ B 激活有助于血管紧张素 II 诱导的高血压的神经体液兴奋
DOI：
10.1093/cvr/cvp073
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发表时间：
2009-06-01
影响因子：
10.8
通讯作者：
Francis, Joseph
中科院分区：
文献类型：
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作者：
Kang, Yu-Ming;Ma, Ying;Francis, Joseph
血管紧张素II（ANG II）诱导的炎症和氧化应激反应有助于高血压的发病机制。在这项研究中，我们确定核因子-κ B（NF-κ B B）激活下丘脑室旁核（PVN）是否增加氧化应激，并有助于ANG II诱导的高血压反应。这些大鼠接受载体或氯沙坦（LOS，20 μ g/h），血管紧张素II 1型受体（AT 1-R）拮抗剂;吡咯烷二硫代氨基甲酸酯（PDTC，5 μ g/h），NF-κ B抑制剂; tempol（TEMP，80 μ g/h），超氧化物清除剂; LOS（20 μ g/h）和PDTC（5 μ g/h）;或TEMP（80 μ g/h）和PDTC（5 μ g/h），通过渗透微型泵脑室内（ICV）给药。ANG II输注导致平均动脉压、肾交感神经活性、血浆促炎细胞因子（PIC）、去甲肾上腺素和醛固酮升高。与对照组相比，这些大鼠的室旁核中Fra-LI（慢性神经元激活的指标）、PIC、磷酸化IKK β、NF-κ B亚单位、AT 1-R、超氧化物和gp 91（phox）（NADP（H）氧化酶的亚单位）水平也较高，I κ B α水平较低。用LOS、PDTC或TEMP进行ICV治疗可减弱这些变化，而用ICV LOS和PDTC或ICV TEMP和PDTC联合治疗可预防这些ANG II诱导的高血压反应。这些结果表明，ANG II诱导的脑内肾素-血管紧张素系统增加可激活PVN中的NF-κ B B，并有助于高血压的交感兴奋。室旁核中超氧化物的增加有助于高血压时NF-κ B B活化和神经体液兴奋。
Angiotensin II (ANG II)-induced inflammatory and oxidative stress responses contribute to the pathogenesis of hypertension. In this study, we determined whether nuclear factor-kappa B (NF-kappa B) activation in the hypothalamic paraventricular nucleus (PVN) increases oxidative stress and contributes to the ANG II-induced hypertensive response.Rats were infused intravenously with ANG II (10 ng/kg per min) or saline for 4 weeks. These rats received either vehicle or losartan (LOS, 20 mu g/h), an angiotensin II type 1 receptor (AT1-R) antagonist; pyrrolidine dithiocarbamate (PDTC, 5 mu g/h), a NF-kappa B inhibitor; tempol (TEMP, 80 mu g/h), a superoxide scavenger; LOS (20 mu g/h), and PDTC (5 mu g/h); or TEMP (80 mu g/h) and PDTC (5 mu g/h), given intracerebroventricularly (ICV) via osmotic minipump. ANG II infusion resulted in increased mean arterial pressure, renal sympathetic nerve activity, plasma proinflammatory cytokines (PIC), norepinephrine, and aldosterone. These rats also had higher levels of Fra-LI (an indicator of chronic neuronal activation), PIC, phosphorylated IKK beta, NF-kappa B subunits, AT1-R, superoxide, and gp91(phox) (a subunit of NADP(H) oxidase) and lower levels of I kappa B alpha in the PVN than control animals. ICV treatment with LOS, PDTC, or TEMP attenuated these changes, and combined treatment with ICV LOS and PDTC, or ICV TEMP and PDTC prevented these ANG II-induced hypertensive responses.These findings suggest that an ANG II-induced increase in the brain renin-angiotensin system activates NF-kappa B in the PVN and contributes to sympathoexcitation in hypertension. The increased superoxide in the PVN contributes to NF-kappa B activation and neurohumoral excitation in hypertension.