Mechanisms of renal sympathetic activation in renovascular hypertension
Mechanisms of renal sympathetic activation in renovascular hypertension
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DOI：
10.1113/expphysiol.2014.079855
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发表时间：
2015-05-01
影响因子：
2.7
通讯作者：
Bergamaschi, Cassia T.
中科院分区：
文献类型：
--
作者：
Campos, Ruy R.;Oliveira-Sales, Elizabeth Barbosa;Bergamaschi, Cassia T.
本次审查的主题是什么？本文综述了肾血管性高血压时交感神经兴奋的潜在机制，重点讨论室旁核和延髓头端腹外侧区氧化应激增加的重要性。肾血管损伤后系统性高血压的主要原因是肾功能紊乱还是自主神经功能紊乱仍有争议。在这里，我们通过描述肾脏和大脑之间的串扰采取综合方法。我们展示了如何在中枢神经系统的变化，特别是在交感神经前运动神经元，激活缺血性肾脏疾病的实验模型renovascularhypertension.This审查涉及的交感神经兴奋在renovascularhypertension. This潜在的机制。我们专注于增加氧化应激下丘脑室旁核（PVN）和延髓头端腹外侧区（RVLM）的自主神经功能障碍与肾血管性高血压在两肾，一夹（2K-1C）模型的重要性。我们发现在2K-1C大鼠，夹闭后6周，RVLM和PVN内血管紧张素II 1型受体的mRNA和蛋白表达显著增加。此外，NADPH氧化酶亚基（p47 phox和gp 91 phox）的mRNA在2K-1C大鼠RVLM和PVN中的表达高于假手术组。然而，铜锌超氧化物歧化酶在这些地区的基因表达没有改变，这表明过量生产的活性氧自由基破坏任何内源性抗氧化系统的RVLM和PVN在肾血管性高血压。事实上，Tempol或维生素C（静脉注射或直接注射到PVN或RVLM）的急性给药导致2K-1C大鼠的血压和肾交感神经活动显著降低，但在对照组动物中没有。因此，我们认为，血管紧张素II和氧化应激引发的RVLM和PVN神经元的活动增加是一个主要的机制参与维持交感神经兴奋的心血管系统在肾血管性高血压。
What is the topic of this review? This review addresses the underlying mechanisms involved in sympathoexcitation during renovascular hypertension, focusing on the importance of increased oxidative stress in the paraventricular nucleus and rostral ventrolateral medulla.What advances does it highlight? Whether renal or autonomic dysfunction is the major contributor to systemic hypertension following a renovascular insult is still a matter of debate. Here, we take an integrative approach by describing the crosstalk between the kidney and brain. We show how changes in the CNS, and in sympathetic premotor neurons in particular, are activated by ischaemic renal disease in an experimental model of renovascular hypertension.This review addresses the underlying mechanisms involved in the sympathoexcitation in renovascular hypertension. We focus on the importance of increased oxidative stress in the paraventricular nucleus of hypothalamus (PVN) and rostral ventrolateral medulla (RVLM) for the autonomic dysfunction associated with renovascular hypertension in the two-kidney, one-clip (2K-1C) model. We found in 2K-1C rats, 6weeks after clipping, a significant increase in the mRNA and protein expression of the angiotensinII type1 receptor within the RVLM and PVN. In addition, mRNA from NADPH oxidase subunits (p47phox and gp91phox) was greater in the RVLM and PVN of 2K-1C rats than in a sham-operated group. However, CuZn superoxide dismutase gene expression in these regions was not changed, suggesting that excessive production of reactive oxygen species overwhelms any endogenous antioxidant system in the RVLM and PVN in renovascular hypertension. In fact, acute administration of tempol or vitaminC (either i.v. or directly into the PVN or RVLM) caused a significant decrease in blood pressure and renal sympathetic nerve activity in 2K-1C rats, but not in control animals. Thus, we suggest that an increase in the activity of RVLM and PVN neurons triggered by angiotensinII and oxidative stress is a major mechanism involved in the maintenance of sympathoexcitation of the cardiovascular system in renovascular hypertension.