Editorial Focus: the brain renin-angiotensin system and hypertension. Focus on: hypertension in mice with transgenic activation of the brain renin-angiotensin system is vasopressin dependent.
Editorial Focus: the brain renin-angiotensin system and hypertension. Focus on: hypertension in mice with transgenic activation of the brain renin-angiotensin system is vasopressin dependent.
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编辑焦点：大脑肾素-血管紧张素系统和高血压。
DOI：
10.1152/ajpregu.00272.2013
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Cunningham,JThomas
中科院分区：
文献类型：
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作者：
Cunningham,JThomas
脑肾素-血管紧张素系统(RAS)因其在中枢心血管调节和体液稳态中的作用而被广泛研究。这一系统的许多早期工作都受到Brody，Johnson和他的同事的开创性工作的刺激，他们专注于循环中的血管紧张素II和促进神经源性高血压的脑RAS之间可能的相互作用。我们目前对脑RAS的了解已经发展到包括多种神经活性多肽，它们不仅在高血压的背景下，而且在充血性心力衰竭、胎儿程序性心血管疾病和衰老(2，4，7，8)的背景下，对自主神经系统的调节具有不同的作用。在我们对这一系统的复杂性的理解中，许多进展都是新的转基因方法的结果，这种方法允许组织特异性地表达或删除RAS的重要成分。在Littlejohn等人最近发表的文章中(5)，一个复杂的双转基因小鼠模型被用来检测选择性激活脑RAS系统对血压和水和电解质稳态的影响。在这个模型中，通过结合两个单独的小鼠模型来选择性地针对大脑：一个是由神经元特异性启动子突触素驱动的人肾素选择性过表达，另一个是由其自身的启动子驱动的人血管紧张素原的过度表达。由于物种的特异性，RAS的激活仅限于同时发生两种转基因的区域。以前对该模型的研究表明能量代谢改变、液体周转增加和高血压(3)。在最近的研究中，研究人员探索了在该模型中调节液体平衡变化的机制，这导致了一系列关于高血压潜在机制的有趣观察。在双转基因小鼠中，作者观察到下丘脑视上核加压素阳性图谱的数量增加，并伴有显著的低钠血症。尽管在转基因小鼠中，血管加压素前体循环中的铜绿素减少，但尿铜蛋白排泄量显著增加，这表明大脑RAS活性的增加刺激了血管加压素的释放。转基因小鼠的血压显着升高，通过长期输注非特异性加压素拮抗剂康尼普坦后血压恢复正常。对这些影响的进一步研究表明血管减少
The brain renin-angiotensin system (RAS) has been extensively studied due to its role in central cardiovascular regulation and body fluid homeostasis. Much of the early work on this system was stimulated by the pioneering work of Brody, Johnson, and colleagues (1) who focused on possible interactions between circulating angiotensin II and a brain RAS promoting neurogenic hypertension. Our current understanding of the brain RAS has evolved to include multiple neuroactive peptides that have differential effects in regulating of the autonomic nervous system not only in the context of hypertension but also in congestive heart failure, fetal programed cardiovascular disease, and aging (2, 4, 7, 8). Many of the advances in our understanding of the complexity of this system have been the result of new transgenic approaches that permit tissue-specific expression or deletion of important components of RAS.In the recent publication by Littlejohn et al.(5), a sophisticated double transgenic mouse model was used to examine the effects of selective activation of the brain RAS system on blood pressure and water and electrolyte homeostasis. In this model, the brain is selectively targeted by combining two separate mouse models: one with selective overexpression of human renin driven by the neuron-specific promoter synapsin and another with human angiotensinogen driven by its own promoter. Because of the species specificity, activation of the RAS is restricted to regions where both transgenes occur. Previous studies with this model demonstrated alterations in energy metabolism, increased fluid turnover, and hypertension (3). In the more recent study, the investigators explored the mechanism mediating the changes in fluid balance produced in this model, which has led to a series of interesting observations about the mechanisms underlying the hypertension. In the double transgenic mice, the authors observed an increase in the numbers of vasopressin-positive profiles in the supraoptic nucleus of the hypothalamus along with a significant hyponatremia. Although circulating copeptin, a vasopressin prosegment, was decreased in the transgenic mice, urinary copeptin excretion was significantly elevated, suggesting that increased activity of the brain RAS was stimulating vasopressin release. The transgenic mice displayed a significant elevation in blood pressure that was normalized by chronic infusions of a nonspecific vasopressin antagonist conivaptan. Further investigation of these effects demonstrated decreased vascular