Desideri Giovambattista, Bravi Maria Cristina, Tucci Marzia, Croce Giuseppe, Marinucci Maria Contina, Santucci Anna, Alesse Edoardo, Ferri Claudio
Department of Internal Medicine and Public Health, University of L'Aquila, Via Vetoio, Blocco 11, 67100, Coppito, L'Aquila, Italy.
Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1218-23. doi: 10.1161/01.ATV.0000078521.51319.65. Epub 2003 May 22.
The migratory capability of vascular endothelial cells plays a pivotal role in the maintenance of vessel wall integrity and is stimulated by nitric oxide (NO). Angiotensin II increases NAD(P)H oxidase activity in endothelial cells, thereby promoting reactive oxygen species (ROS) generation. Because ROS can both reduce NO synthase activity and increase NO breakdown, thus impairing NO availability in endothelial cells, we evaluated the effect of angiotensin II on human vascular endothelial cell (HUVEC) motility.
Angiotensin II dose- and time-dependently reduced HUVEC migration. Besides inhibiting HUVEC motility, angiotensin II altered intracellular glutathione redox status. The generation of ROS by cultured HUVECs was significantly increased by angiotensin II. Furthermore, angiotensin II reduced NO metabolite concentrations in culture media. The angiotensin II type 1 receptor antagonist candesartan cilexetil attenuated the inhibitory action exerted by angiotensin II on HUVEC motility, reversed the angiotensin II-induced increase in intracellular oxidative stress, and restored NO availability. Similar effects were exerted by the flavonoid inhibitor diphenylene iodinium and the antioxidant agent N-acetyl-L-cysteine.
All together, our data demonstrate that angiotensin II inhibits HUVEC motility by reducing NO availability. Such reduction is due to an angiotensin II type 1 receptor-dependent increment in intracellular ROS generation.
血管内皮细胞的迁移能力在维持血管壁完整性中起关键作用，且受一氧化氮（NO）刺激。血管紧张素II可增加内皮细胞中NAD(P)H氧化酶活性，从而促进活性氧（ROS）生成。由于ROS既能降低一氧化氮合酶活性又能增加NO分解，进而损害内皮细胞中NO的可用性，我们评估了血管紧张素II对人血管内皮细胞（HUVEC）迁移的影响。
血管紧张素II剂量和时间依赖性地降低HUVEC迁移。除了抑制HUVEC运动性外，血管紧张素II还改变了细胞内谷胱甘肽氧化还原状态。血管紧张素II显著增加了培养的HUVEC产生的ROS。此外，血管紧张素II降低了培养基中NO代谢物浓度。血管紧张素II 1型受体拮抗剂坎地沙坦酯减弱了血管紧张素II对HUVEC运动性的抑制作用，逆转了血管紧张素II诱导的细胞内氧化应激增加，并恢复了NO的可用性。类黄酮抑制剂二苯基碘鎓和抗氧化剂N-乙酰-L-半胱氨酸也有类似作用。
总之，我们的数据表明血管紧张素II通过降低NO可用性来抑制HUVEC运动性。这种降低是由于血管紧张素II 1型受体依赖性细胞内ROS生成增加所致。
