Cross-talk between cytokines and renin-angiotensin in hypothalamic paraventricular nucleus in heart failure:: role of nuclear factor-κB
Cross-talk between cytokines and renin-angiotensin in hypothalamic paraventricular nucleus in heart failure:: role of nuclear factor-κB
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DOI：
10.1093/cvr/cvn119
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发表时间：
2008-09-01
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
核因子-κ B（NF-κ B）是一种强有力的细胞因子。心血管疾病中促炎细胞因子（PIC）和氧化应激诱导剂。在这项研究中，我们确定是否上调NF-κ B B在下丘脑室旁核（PVN）直接或通过与肾素-血管紧张素系统（RAS）的相互作用，在心脏衰竭（HF）。方法和结果大鼠植入脑室内（ICV）插管和冠状动脉结扎，或假手术（SHAM）。随后，用血管紧张素1型受体（AT 1-R）拮抗剂氯沙坦（LOS，20 μ g/h）或SN 50（2 μ g/h）（其抑制NF-κ B的核转位）或tempol（TEMP，80 μ g/h）（一种膜可渗透的超氧化物清除剂）或溶媒对动物进行ICV处理4周。HF诱导室旁核中AT 1-R、PIC、NAD（P）H氧化酶基因和NF-κ B B p50的表达显著增加，血浆去甲肾上腺素（NE）水平显著升高。相反，与溶剂处理的HF大鼠相比，ICV LOS、SN 50或TEMP减弱了PVN中的PIC、NF-κ B p50、AT 1-R和NAD（P）H氧化酶基因。LOS，SN 50，或TEMP治疗也降低了NE，血管紧张素11和PIC的血浆水平，并降低左心室舒张末期pressure.Conclusion这些研究结果表明，NF-κ B介导的RAS和PIC之间的串扰在室旁核HF，和超氧化物刺激更多的NF-κ B在室旁核，有助于神经体液兴奋。
Aims Nuclear factor-kappa B (NF-kappa B) is a potent. inducer of pro-inflammatory cytokines (PIC) and oxidative stress in cardiovascular disease. In this study, we determined whether upregutation of NF-kappa B in the hypothalamic paraventricular nucleus (PVN) contributed to neurohumoral excitation either directly, or via interaction with the renin-angiotensin system (RAS), in heart failure (HF).Methods and results Rats were implanted with intracerebroventricular (ICV) cannulae and subjected to coronary artery ligation, or sham surgery (SHAM). Subsequently, animals were ICV treated with the angiotensin type 1 receptor (AT1 -R) antagonist losartan (LOS, 20 mu g/h), or SN50 (2 mu g/h), which inhibits nuclear translocation of NF-kappa B, or tempol (TEMP, 80 mu g/h), a membrane-permeable superoxide scavenger, or vehicle for 4 weeks. HF induced a significant increase in the expression of AT1-R, PIC, and NAD(P)H oxidase genes and NF-kappa B p50 in the PVN and in plasma norepinephrine (NE) levels when compared with SHAM rats. In contrast, ICV LOS, SN50, or TEMP attenuated PIC, NF-kappa B p50, AT1-R and NAD(P)H oxidase genes in the PVN compared with vehicle-treated HF rats. Treatment with LOS, SN50, or TEMP also reduced plasma levels of NE, angiotensin 11, and PIC, and decreased left ventricular end diastolic pressure.Conclusion These findings indicate that NF-kappa B mediates the cross-talk between RAS and PIC in the PVN in HF, and that superoxide stimulates more NF-kappa B in the PVN and contributes to neurohumoral excitation.