The arcuate nucleus: A site of synergism between Angiotensin II and leptin to increase sympathetic nerve activity and blood pressure in rats.
The arcuate nucleus: A site of synergism between Angiotensin II and leptin to increase sympathetic nerve activity and blood pressure in rats.
复制标题
弓状核：血管紧张素 II 和瘦素之间的协同作用位点，可增加大鼠的交感神经活动和血压。
DOI：
10.1016/j.neulet.2022.136773
复制
发表时间：
2022
影响因子：
2.5
通讯作者：
Brooks,VirginiaL
中科院分区：
文献类型：
--
作者：
Shi,Zhigang;Stornetta,RuthL;Stornetta,DanielS;Abbott,StephenBG;Brooks,VirginiaL
大脑中瘦素增加交感神经活动（SNA）和血压的作用取决于功能性血管紧张素II（AngII）1a型受体（AT 1aR）;然而，相互作用的位点和机制尚不清楚。在这里，我们确定了一个网站，下丘脑弓状核（ArcN），因为在麻醉的雄性大鼠中使用氯沙坦或坎地沙坦在ArcN中预先局部阻断AT 1aR基本上消除了对ArcN瘦素纳米注射的交感兴奋和升压反应。与小鼠不同，在雄性和雌性大鼠中，AT 1aR和LepR很少共同定位，这表明这种相互依赖性通过局部中间神经元或神经元网络间接发生。ArcN瘦素通过激活前阿黑皮素（POMC）输入到PVN来增加SNA，但这种激活需要同时抑制紧张性PVN神经肽Y（NPY）交感神经抑制。由于AngII-AT 1aR抑制ArcN NPY神经元，我们提出，AT 1aR抑制NPY块瘦素诱导的SNA增加的损失;换句话说，ArcN-AngII-AT 1aR是瘦素诱导的交感兴奋的看门人。随着肥胖，瘦素和血管生成素II增加;因此，增加的AT 1aR激活可以打开大门，允许瘦素（和胰岛素）驱动交感神经兴奋不减弱，导致高血压。
The action of leptin in brain to increase sympathetic nerve activity (SNA) and blood pressure depends upon functional Angiotensin II (AngII) type 1a receptors (AT1aR); however, the sites and mechanism of interaction are unknown. Here we identify one site, the hypothalamic arcuate nucleus (ArcN), since prior local blockade of AT1aR in the ArcN with losartan or candesartan in anesthetized male rats essentially eliminated the sympathoexcitatory and pressor responses to ArcN leptin nanoinjections. Unlike mice, in male and female rats, AT1aR and LepR rarely co-localized, suggesting that this interdependence occurs indirectly, via a local interneuron or network of neurons. ArcN leptin increases SNA by activating pro-opiomelanocortin (POMC) inputs to the PVN, but this activation requires simultaneous suppression of tonic PVN Neuropeptide Y (NPY) sympathoinhibition. Because AngII-AT1aR inhibits ArcN NPY neurons, we propose that loss of AT1aR suppression of NPY blocks leptin-induced increases in SNA; in other words, ArcN-AngII-AT1aR is a gatekeeper for leptin-induced sympathoexcitation. With obesity, both leptin and AngII increase; therefore, the increased AT1aR activation could open the gate, allowing leptin (and insulin) to drive sympathoexcitation unabated, leading to hypertension.