Department of Internal Medicine, University of Iowa, Iowa City, 52242, USA.
Cell Metab. 2010 Nov 3;12(5):431-42. doi: 10.1016/j.cmet.2010.09.011.
The renin-angiotensin system (RAS), in addition to its endocrine functions, plays a role within individual tissues such as the brain. The brain RAS is thought to control blood pressure through effects on fluid intake, vasopressin release, and sympathetic nerve activity (SNA), and may regulate metabolism through mechanisms which remain undefined. We used a double-transgenic mouse model that exhibits brain-specific RAS activity to examine mechanisms contributing to fluid and energy homeostasis. The mice exhibit high fluid turnover through increased adrenal steroids, which is corrected by adrenalectomy and attenuated by mineralocorticoid receptor blockade. They are also hyperphagic but lean because of a marked increase in body temperature and metabolic rate, mediated by increased SNA and suppression of the circulating RAS. β-adrenergic blockade or restoration of circulating angiotensin-II, but not adrenalectomy, normalized metabolic rate. Our data point to contrasting mechanisms by which the brain RAS regulates fluid intake and energy expenditure.
肾素-血管紧张素系统（RAS）除了具有内分泌功能外，在大脑等单个组织中也发挥作用。大脑 RAS 被认为通过对液体摄入、血管加压素释放和交感神经活动（SNA）的影响来控制血压，并且可能通过尚未确定的机制来调节代谢。我们使用了一种表现出大脑特异性 RAS 活性的双转基因小鼠模型，以研究有助于液体和能量稳态的机制。这些小鼠通过增加肾上腺类固醇表现出高液体周转率，这可通过肾上腺切除术纠正，并可通过阻断盐皮质激素受体而减弱。它们还表现出多食但消瘦，因为体温和代谢率显著增加，这是通过增加 SNA 和抑制循环 RAS 介导的。β-肾上腺素能阻断或循环血管紧张素-II 的恢复，但不是肾上腺切除术，可使代谢率正常化。我们的数据表明，大脑 RAS 调节液体摄入和能量消耗的机制是不同的。
