Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
Cardiovasc Res. 2010 Aug 1;87(3):578-84. doi: 10.1093/cvr/cvq059. Epub 2010 Mar 3.
Angiotensin(1-7) (Ang1-7) acting at the level of the rostral ventrolateral medulla (RVLM) affects arterial pressure. The cellular substrate of Ang1-7 remains unknown. We sought to determine which cell types in RVLM could mediate its actions and whether these are altered in the spontaneously hypertensive rat (SHR).
Astrocytes, catecholaminergic (CA-ergic) and non-CA-ergic neurones were targeted with adenoviral vectors in organotypic slice cultures from Wistar rats and SHR. Astrocytic Ca(2+) signalling was monitored using a genetically engineered Ca(2+) sensor Case12. CA-ergic neurones expressed enhanced green fluorescent protein (EGFP) under control of the PRS x 8 promoter, whereas non-CA-neurones expressed EGFP under control of the synapsin-1 promoter. Neurones were recorded in whole cell mode while Ca(2+) was monitored using Rhod-2. RVLM astrocytes responded to Ang1-7 (200-1000 nM) with concentration-dependent Ca(2+) elevation. In SHR, the response to 1000 nM was significantly attenuated. The competitive Ang1-7 receptor antagonist A779, but not the AT(1) receptor blocker (losartan), suppressed Ang1-7-induced Ca(2+) elevations, which were also antagonized by blocking intracellular Ca(2+) stores. Ang1-7 evoked no consistent changes in Ca(2+) or membrane excitability in CA-ergic or non-CA-ergic neurones in either rat strain.
Astroglia are a plausible cellular target of Ang1-7 in RVLM. Our data suggest that astrocytic responsiveness to Ang1-7 is reduced in SHR. We hypothesise that Ang1-7 modulates astrocytic signalling which in vivo may affect local metabolism and microcirculation, resulting in changes in activity of RVLM pre-sympathetic neurones and hence blood pressure.
血管紧张素(1-7)(Ang1-7)在延髓头端腹外侧区(RVLM)水平发挥作用，影响动脉血压。Ang1-7 的细胞基质仍不清楚。我们试图确定 RVLM 中的哪些细胞类型可以介导其作用，以及这些作用在自发性高血压大鼠(SHR)中是否发生改变。
在 Wistar 大鼠和 SHR 的器官型切片培养物中，用腺病毒载体靶向星形胶质细胞、儿茶酚胺能(CA-ergic)和非 CA-ergic 神经元。使用基因工程 Ca(2+)传感器 Case12 监测星形胶质细胞 Ca(2+)信号。CA-ergic 神经元在 PRS x 8 启动子的控制下表达增强型绿色荧光蛋白(EGFP)，而非 CA-ergic 神经元在突触素-1 启动子的控制下表达 EGFP。神经元在全细胞模式下记录，同时使用 Rhod-2 监测Ca(2+)。RVLM 星形胶质细胞对 Ang1-7(200-1000 nM)的反应呈浓度依赖性Ca(2+)升高。在 SHR 中，对 1000 nM 的反应明显减弱。竞争性 Ang1-7 受体拮抗剂 A779，但不是 AT(1)受体阻滞剂(洛沙坦)，抑制 Ang1-7 诱导的Ca(2+)升高，这些升高也被阻断细胞内 Ca(2+)储存所拮抗。在两种大鼠品系中，Ang1-7 都没有引起 CA-ergic 或非 CA-ergic 神经元的Ca(2+)或膜兴奋性的一致变化。
星形胶质细胞是 RVLM 中 Ang1-7 的一个可能的细胞靶标。我们的数据表明，SHR 中星形胶质细胞对 Ang1-7 的反应性降低。我们假设 Ang1-7 调节星形胶质细胞信号，在体内可能影响局部代谢和微循环，从而改变 RVLM 交感前神经元的活动，进而影响血压。
