Department of Neurosciences, Université de Montréal, 2960 Chemin de la Tour, Montréal, Québec, H3T 1J4, Canada.
Groupe de recherche sur le système nerveux central (GRSNC), Université de Montréal, 2960 Chemin de la Tour, Montréal, Québec, H3T 1J4, Canada.
J Neuroinflammation. 2018 Feb 28;15(1):62. doi: 10.1186/s12974-018-1090-z.
Angiotensin II (Ang II), a peptide hormone involved in the development of hypertension, causes systemic and cerebral inflammation, affecting brain regions important for blood pressure control. The cause-and-effect relationship between hypertension and inflammation is two-way, but the role of blood pressure in the induction of cerebral inflammation is less clear. The vulnerability of specific brain regions, particularly those important for memory, is also of interest.
We used molecular biology approaches, immunohistochemistry, and electron microscopy to examine the interdependence between the hypertensive and pro-inflammatory effects of Ang II. We examined the effect of blood pressure by administering a subpressive (200 ng/kg/min) or a pressive Ang II dose (1000 or 1900 ng/kg/min) with and without hydralazine (150 mg/L) for 1 week and used phenylephrine to increase blood pressure independently of the renin-angiotensin system.
Ang II increased ionized calcium-binding adaptor molecule 1 (Iba-1) levels (marker of microgliosis) in the whole brain and in the hippocampus in a dose-dependent manner. Pressive Ang II induced specific changes in microglial morphology, indicating differences in functional phenotype. An increase in hippocampal glial fibrillary acidic protein (GFAP) was seen in mice receiving pressive Ang II, while no induction of cerebral gliosis was observed after 7 days of subpressive Ang II infusion. Although phenylephrine led to increased astrogliosis, it did not affect Iba-1 expression. Pressive Ang II stimulated TNF-α production in the hippocampus, and daily treatment with hydralazine prevented this increase. Hydralazine also reduced GFAP and Iba-1 levels. With longer perfusion (14 days), subpressive Ang II led to some but not all the inflammatory changes detected with the pressive doses, mainly an increase in CD68 and Iba-1 but not of GFAP or TNF-α.
Blood pressure and Ang II differentially contribute to hippocampal inflammation in mice. Control of blood pressure and Ang II levels should prevent or reduce brain inflammation and therefore brain dysfunctions associated with hypertension.
血管紧张素 II（Ang II）是一种参与高血压发展的肽类激素，可引起全身和脑内炎症，影响血压控制的重要脑区。高血压和炎症之间的因果关系是双向的，但血压在诱导脑内炎症中的作用尚不清楚。特定脑区的易感性，特别是对记忆重要的脑区，也很重要。
我们使用分子生物学方法、免疫组织化学和电子显微镜检查了 Ang II 的高血压和促炎作用之间的相互依赖性。我们通过给予亚降压（200 ng/kg/min）或降压 Ang II 剂量（1000 或 1900 ng/kg/min）以及是否给予肼屈嗪（150 mg/L）来检查血压的影响，并用去氧肾上腺素独立于肾素-血管紧张素系统来增加血压。
Ang II 以剂量依赖性方式增加了全脑和海马中的离子钙结合衔接蛋白 1（Iba-1）水平（小胶质细胞增生的标志物）。降压 Ang II 诱导小胶质细胞形态发生特定变化，表明功能表型存在差异。在接受降压 Ang II 的小鼠中，海马中的神经胶质纤维酸性蛋白（GFAP）增加，而在亚降压 Ang II 输注 7 天后未观察到脑内神经胶质增生。虽然去氧肾上腺素导致星形胶质细胞增生，但不影响 Iba-1 表达。降压 Ang II 刺激海马中的 TNF-α产生，而每日给予肼屈嗪可防止这种增加。肼屈嗪还降低了 GFAP 和 Iba-1 水平。随着灌注时间延长（14 天），亚降压 Ang II 导致了用降压剂量检测到的一些但不是所有的炎症变化，主要是 CD68 和 Iba-1 的增加，但 GFAP 或 TNF-α没有增加。
血压和 Ang II 对小鼠海马炎症有不同的贡献。控制血压和 Ang II 水平应可预防或减少与高血压相关的脑炎症和脑功能障碍。
