Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
Molecular Medicine Graduate Program, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
Physiol Genomics. 2017 Dec 1;49(12):722-732. doi: 10.1152/physiolgenomics.00087.2017. Epub 2017 Oct 6.
The renin-angiotensin system (RAS), originally described as a circulating hormone system, is an enzymatic cascade in which the final vasoactive peptide angiotensin II (ANG) regulates cardiovascular, hydromineral, and metabolic functions. The RAS is also synthesized locally in a number of tissues including the brain, where it can act in a paracrine fashion to regulate blood pressure, thirst, fluid balance, and resting energy expenditure/resting metabolic rate (RMR). Recent studies demonstrate that ANG AT receptors () specifically in agouti-related peptide (AgRP) neurons of the arcuate nucleus (ARC) coordinate autonomic and energy expenditure responses to various stimuli including deoxycorticosterone acetate (DOCA)-salt, high-fat feeding, and leptin. It remains unclear, however, how these disparate stimuli converge upon and activate this specific population of AT receptors in AgRP neurons. We hypothesize that these stimuli may act to stimulate local expression of the angiotensinogen (AGT) precursor for ANG, or the expression of AT receptors, and thereby local activity of the RAS within the (ARC). Here we review mechanisms that may control AGT and AT expression within the central nervous system, with a particular focus on mechanisms activated by steroids, dietary fat, and leptin.
肾素-血管紧张素系统（RAS）最初被描述为一种循环激素系统，是一种酶级联反应，其中最终的血管活性肽血管紧张素 II（ANG）调节心血管、水盐和代谢功能。RAS 也在包括大脑在内的许多组织中局部合成，在那里它可以以旁分泌的方式发挥作用，调节血压、口渴、液体平衡和静息能量消耗/静息代谢率（RMR）。最近的研究表明，ANG AT 受体（）在弓状核（ARC）的刺鼠相关肽（AgRP）神经元中特异性表达，协调自主神经和能量消耗对各种刺激的反应，包括去氧皮质酮醋酸盐（DOCA）-盐、高脂肪喂养和瘦素。然而，目前尚不清楚这些不同的刺激因素如何集中并激活 AgRP 神经元中这一特定的 AT 受体群体。我们假设这些刺激因素可能作用于刺激 ANG 的血管紧张素原（AGT）前体或 AT 受体的表达，从而在（ARC）内局部激活 RAS 的活性。在这里，我们回顾了可能控制中枢神经系统中 AGT 和 AT 表达的机制，特别关注类固醇、膳食脂肪和瘦素激活的机制。
