Institute of Fetology, First Hospital of Soochow University, Suzhou, China.
Institute of Fetology, First Hospital of Soochow University, Suzhou, China
J Am Heart Assoc. 2017 Oct 3;6(10):e006630. doi: 10.1161/JAHA.117.006630.
Hypoxia during pregnancy could cause abnormal development and lead to increased risks of vascular diseases in adults. This study determined angiotensin II (AII)-mediated vascular dysfunction in offspring middle cerebral arteries (MCA).
Pregnant rats were subjected to hypoxia. Vascular tension in offspring MCA by AII with or without inhibitors, calcium channel activities, and endoplasmic reticulum calcium stores were tested. Whole-cell patch clamping was used to investigate voltage-dependent calcium channel currents. mRNA expression was tested using quantitative real-time polymerase chain reaction. AII-mediated MCA constriction was greater in male offspring exposed to prenatal hypoxia. AT1 and AT2 receptors were involved in the altered AII-mediated vasoconstriction. Prenatal hypoxia increased baseline activities of L-type calcium channel currents in MCA smooth muscle cells. However, calcium currents stimulated by AII were not significantly changed, whereas nifedipine inhibited AII-mediated vasoconstrictions in the MCA. Activities of IP/ryanodine receptor-operated calcium channels, endoplasmic reticulum calcium stores, and sarcoendoplasmic reticulum membrane Ca-ATPase were increased. Prenatal hypoxia also caused dysfunction of vasodilatation via the endothelium NO synthase. The mRNA expressions of AT1A, AT1B, AT2R, Cav1.2α1C, Cav3.2α1H, and ryanodine receptor RyR2 were increased in the prenatal-hypoxia group.
Hypoxia in pregnancy could induce dysfunction in both contraction and dilation in the offspring MCA. AII-increased constriction in the prenatal-hypoxia group was not mainly dependent on the L-type and T-type calcium channels; it might predominantly rely on the AII receptors, IP/ryanodine receptors, and the endoplasmic reticulum calcium store as well as calcium ATPase.
孕期缺氧可导致胎儿发育异常，并增加成年后患血管疾病的风险。本研究旨在探讨血管紧张素 II（AII）介导的胎鼠大脑中动脉（MCA）血管功能障碍。
对孕鼠进行缺氧处理。检测 AII 及其抑制剂对胎鼠 MCA 血管张力、钙通道活性和内质网钙库的影响，应用全细胞膜片钳技术检测电压依赖性钙通道电流，采用实时定量聚合酶链反应检测 mRNA 表达。结果发现，孕期缺氧雄性胎鼠的 MCA 对 AII 介导的收缩反应增强，AII 介导的血管收缩改变涉及 AT1 和 AT2 受体。孕期缺氧增加了 MCA 平滑肌细胞 L 型钙通道电流的基础活性，但 AII 刺激的钙电流无明显变化，而硝苯地平可抑制 MCA 中 AII 介导的血管收缩。IP/ryanodine 受体操纵性钙通道、内质网钙库和肌浆网 Ca-ATP 酶的活性增加。孕期缺氧还导致内皮型一氧化氮合酶介导的血管舒张功能障碍。AII 受体、L 型钙通道、IP/ryanodine 受体和内质网钙库以及钙泵等多种因素可能参与了孕期缺氧诱导的胎鼠 MCA 收缩和舒张功能障碍。
孕期缺氧可导致胎鼠 MCA 收缩和舒张功能障碍。AII 增加的收缩反应主要不依赖于 L 型和 T 型钙通道，可能主要依赖于 AII 受体、IP/ryanodine 受体以及内质网钙库和钙泵。
