Activation of hypothalamic AgRP and POMC neurons evokes disparate sympathetic and cardiovascular responses
Activation of hypothalamic AgRP and POMC neurons evokes disparate sympathetic and cardiovascular responses
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DOI：
10.1152/ajpheart.00411.2020
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发表时间：
2020-11-01
影响因子：
4.8
通讯作者：
Rahmouni, Kamal
中科院分区：
文献类型：
--
作者：
Jiang, Jingwei;Morgan, Donald A.;Rahmouni, Kamal
下丘脑弓状核（ARC）在将外周代谢状态与大脑黑素皮质素系统联系起来方面起着关键作用，黑素皮质素系统影响着包括交感神经系统和血压在内的广泛生理过程。针刺相关肽（AgRP）和促黑素皮质素（POMC）表达神经元是ARC神经元的两种不同分子群，其活性对代谢调节的重要性已得到证实，但它们与交感神经和心血管控制的相关性尚不清楚。我们使用设计物药物（DREADD）技术激活的设计物受体来研究AgRP和POMC神经元的激活如何影响肾交感神经交通和血压。除了剧烈的喂食刺激作用外，redad介导的AgRP激活，而不是POMC神经元，诱导清醒小鼠肾交感神经活动的急性减少。然而，矛盾的是，dreadd介导的AgRP神经元的慢性激活导致血压显著升高，特别是在无活性光期。另一方面，POMC神经元的慢性激活导致血压显著降低。这些结果为ARC AgRP和POMC神经元活动在自主神经和心血管调节中的作用带来了新的见解。弓形核表达agouti相关肽（AgRP）和proopiomelanocortin （POMC）的神经元是控制各种生理过程的脑黑素皮质素系统的重要组成部分。在这里，我们测试了直接激活这两种神经元对代谢和心血管的影响。我们的研究结果表明，除了食物摄入的刺激，化学发生介导的下丘脑弓状核AgRP的激活，而不是POMC，神经元减少肾脏交感交通。尽管如此，AgRP神经元的慢性激活会增加血压。然而，POMC神经元的慢性激活导致血压显著降低。我们的发现强调了弓形核AgRP和POMC神经元活动在自主神经和心血管调节中的重要性。
The arcuate nucleus of the hypothalamus (ARC) plays a key role in linking peripheral metabolic status to the brain melanocortin system, which influences a wide range of physiological processes including the sympathetic nervous system and blood pressure. The importance of the activity of agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons, two molecularly distinct populations of ARC neurons, for metabolic regulation is well established, but their relevance for sympathetic and cardiovascular control remains unclear. We used designer receptors exclusively activated by designer drug (DREADD) technology to study how activation of AgRP and POMC neurons affect renal sympathetic nerve traffic and blood pressure. In addition to the drastic feeding-stimulatory effect, DREADD-mediated activation of AgRP, but not POMC neurons, induced an acute reduction in renal sympathetic nerve activity in conscious mice. Paradoxically, however, DREADD-mediated chronic activation of AgRP neurons caused a significant increase in blood pressure specifically in the inactive light phase. On the other hand, chronic activation of POMC neurons led to a significant reduction in blood pressure. These results bring new insights to a previously unappreciated role of ARC AgRP and POMC neuronal activity in autonomic and cardiovascular regulation.NEW & NOTEWORTHY Agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons of the arcuate nucleus are essential components of the brain melanocortin system that controls various physiological processes. Here, we tested the metabolic and cardiovascular effects of direct activation of these two populations of neurons. Our findings show that, in addition to stimulation of food intake, chemogenetic mediated activation of hypothalamic arcuate nucleus AgRP, but not POMC, neurons reduce renal sympathetic traffic. Despite this, chronic activation of AgRP neurons increased blood pressure. However, chronic activation of POMC neurons led to a significant reduction in blood pressure. Our findings highlight the importance of arcuate nucleus AgRP and POMC neuronal activity in autonomic and cardiovascular regulation.