Hood J D, Meininger C J, Ziche M, Granger H J
Microcirculation Research Institute, Texas A&M University Health Science Center, College Station 77843-1114, USA.
Am J Physiol. 1998 Mar;274(3):H1054-8. doi: 10.1152/ajpheart.1998.274.3.H1054.
Vascular endothelial growth factor (VEGF) is an endothelium-specific secreted protein that potently stimulates vasodilation, microvascular hyperpermeability, and angiogenesis. Nitric oxide (NO) is also reported to modulate vascular tone, permeability, and capillary growth. Therefore, we hypothesized that VEGF might regulate endothelial production of NO. The production of nitrogen oxides by human umbilical vein endothelial cells (HUVECs) was measured after 1, 12, 24, and 48 h of incubation with VEGF. VEGF treatment resulted in both an acute (1 h) and chronic (> 24 h) stimulation of NO production. Furthermore, Western and Northern blotting revealed a VEGF-elicited, dose-dependent increase in the cellular content of endothelial cell nitric oxide synthase (ecNOS) message and protein that may account for the chronic upregulation of NO production elicited by VEGF. Finally, endothelial cells pretreated with VEGF for 24 h and subsequently exposed to A-23187 for 1 h produced NO at approximately twice the rate of cells that were not pretreated with VEGF. We conclude that VEGF upregulates ecNOS enzyme and elicits a biphasic stimulation of endothelial NO production.
血管内皮生长因子（VEGF）是一种内皮细胞特异性分泌蛋白，可有效刺激血管舒张、微血管高通透性和血管生成。据报道，一氧化氮（NO）也可调节血管张力、通透性和毛细血管生长。因此，我们推测VEGF可能调节内皮细胞NO的产生。在人脐静脉内皮细胞（HUVECs）与VEGF孵育1、12、24和48小时后，测量其氮氧化物的产生。VEGF处理导致NO产生的急性（1小时）和慢性（>24小时）刺激。此外，蛋白质印迹法和Northern印迹法显示，VEGF引起内皮型一氧化氮合酶（ecNOS）信使和蛋白质的细胞含量呈剂量依赖性增加，这可能解释了VEGF引起的NO产生的慢性上调。最后，用VEGF预处理24小时，随后暴露于A-23187 1小时的内皮细胞产生NO的速率约为未用VEGF预处理的细胞的两倍。我们得出结论，VEGF上调ecNOS酶并引起内皮细胞NO产生的双相刺激。
