Evidence for intraventricular secretion of angiotensinogen and angiotensin by the subfornical organ using transgenic mice
Evidence for intraventricular secretion of angiotensinogen and angiotensin by the subfornical organ using transgenic mice
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DOI：
10.1152/ajpregu.00511.2016
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发表时间：
2017-06-01
影响因子：
2.8
通讯作者：
Cassell, Martin D.
中科院分区：
文献类型：
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作者：
Agassandian, Khristofor;Grobe, Justin L.;Cassell, Martin D.
直接脑室内注射血管紧张素 II (ANG II) 会导致血压、盐和水摄入量增加，可能模仿了内源性机制介导的效应。穹窿下器官（SFO）是脑脊液（CSF）、ANG I 和 ANG II 的潜在来源，因此我们假设 SFO 具有分泌功能。大脑中血管紧张素原 (AGT) 和肾素的内源水平非常低。因此，我们在两种转基因模型中检查了血管紧张素肽和 AGT 在 SFO 中以及 AGT 在 CSF 中的免疫组织化学定位，这两种转基因模型在大脑中过表达人 AGT（A（+）小鼠）或人 AGT（hAGT）和人肾素（SRA 小鼠）。在基线和脑脊液体积耗尽后进行测量。免疫电子显微镜超微结构分析显示，SFO 中表面的 ANG I/ANG II 和 AGT 免疫反应细胞呈空泡状，并直接通向心室。脑脊液的撤出导致脑脊液中 AGT 的增加，同时伴随着 SFO 细胞内 AGT 免疫反应性的大幅下降。我们的数据支持这样的假设：SFO 是一个分泌器官，至少在控制肾素血管紧张素系统的基因在小鼠体内过度表达的情况下，它会释放 AGT 和可能的 ANG I/ANG II 到心室中。
Direct intracerebroventricular injection of angiotensin II (ANG II) causes increases in blood pressure and salt and water intake, presumably mimicking an effect mediated by an endogenous mechanism. The subfornical organ (SFO) is a potential source of cerebrospinal fluid (CSF), ANG I, and ANG II, and thus we hypothesized that the SFO has a secretory function. Endogenous levels of angiotensinogen (AGT) and renin are very low in the brain. We therefore examined the immunohistochemical localization of angiotensin peptides and AGT in the SFO, and AGT in the CSF in two transgenic models that overexpress either human AGT (A(+) mice), or both human AGT (hAGT) and human renin (SRA mice) in the brain. Measurements were made at baseline and following volumetric depletion of CSF. Ultrastructural analysis with immunoelectron microscopy revealed that superficially located ANG I/ANG II and AGT immunoreactive cells in the SFO were vacuolated and opened directly into the ventricle. Withdrawal of CSF produced an increase in AGT in the CSF that was accompanied by a large decline in AGT immunoreactivity within SFO cells. Our data provide support for the hypothesis that the SFO is a secretory organ that releases AGT and possibly ANG I/ANG II into the ventricle at least under conditions when genes that control the reninangiotensin system are overexpressed in mice.