Vascular oxidative stress upregulates angiotensin II type I receptors via mechanisms involving nuclear factor kappa B.
Vascular oxidative stress upregulates angiotensin II type I receptors via mechanisms involving nuclear factor kappa B.
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DOI：
10.3109/10641963.2014.943402
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Banday AA
中科院分区：
文献类型：
--
作者：
Bhatt SR;Lokhandwala MF;Banday AA
氧化应激与高血压的关系是众所周知的。然而，氧化应激在高血压中的因果作用尚不清楚。血管紧张素II型1受体（AT1R）的上调是高血压发病的重要因素。然而，导致这种上调的机制尚不清楚。氧化应激通过激活核因子κB （NFκB）等转录因子调控蛋白表达。本研究旨在验证氧化应激通过NFκB参与人主动脉平滑肌细胞（HASMC）和自发性高血压大鼠（SHR）血管AT1R上调的假说。暴露于氧化应激的HASMC中，AT1R mRNA显著增加。此外，在抗氧化过氧化氢酶或抗NFκB p65亚基siRNA存在的情况下，氧化应激不能上调AT1Rs。为了检测氧化应激和NFκB在高血压中的作用，我们从5周龄至11-12周龄给予NFκB抑制剂吡咯烷二硫代氨基甲酸酯治疗高血压前期SHR。与年龄匹配的Wistar Kyoto （WKY）大鼠相比，在11-12周龄时，SHR表现出NFκB表达增加、AT1R上调和angii诱导的血管收缩加剧。PDTC治疗SHR降低NFκB表达，AT1R表达正常化，Angⅱ诱导血管收缩。更重要的是，PDTC治疗可显著减轻SHR患者的高血压发展。综上所述，血管氧化可以通过nf - κ b参与的机制上调AT1R，并参与高血压的发生。
The association of oxidative stress with hypertension is well known. However, a causal role of oxidative stress in hypertension is unclear. Vascular angiotensin II type 1 receptor (AT1R) upregulation is a prominent contributor to pathogenesis of hypertension. However, the mechanisms causing this upregulation are unknown. Oxidative stress is an important regulator of protein expression via activation of transcription factors such as nuclear factor kappa B (NFκB). The present study was carried out to test the hypothesis that oxidative stress contributes to vascular AT1R upregulation via NFκB in human aortic smooth muscle cells (HASMC) and spontaneously hypertensive rats (SHR). HASMC exposed to oxidative stress exhibited a robust increase in AT1R mRNA in HASMC. Furthermore, oxidative stress failed to upregulate AT1Rs in the presence of either an antioxidant catalase or siRNA against p65 subunit of NFκB. To test the role of oxidative stress and NFκB in hypertension, prehypertensive SHR were treated with NFκB inhibitor pyrrolidine dithiocarbamate from 5 weeks to 11–12 weeks of age. At 11–12 weeks of age, SHR exhibited increased NFκB expression, AT1R upregulation and exaggerated Ang II-induced vasoconstriction as compared to age-matched Wistar Kyoto (WKY) rats. PDTC treatment of SHR lowered NFκB expression, normalized AT1R expression and Ang II-induced vasoconstriction. More importantly, PDTC treatment significantly attenuated hypertension development in SHR. In conclusion, vascular oxidative can upregulate AT1R, via mechanisms involving NFκB, and contribute to the development of hypertension.
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影响因子：
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作者：
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DOI：
10.1124/jpet.105.088062
发表时间：
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影响因子：
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作者：
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通讯作者：
Vaziri, ND