Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium.
Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium.
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DOI：
10.1161/01.cir.95.4.1030
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发表时间：
1997-02
期刊：
影响因子：
37.8
通讯作者：
Rien van der Zee;T. Murohara;Zhengyu Luo;F. Zollmann;J. Passeri;C. Lekutat;J. Isner
中科院分区：
文献类型：
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作者：
Rien van der Zee;T. Murohara;Zhengyu Luo;F. Zollmann;J. Passeri;C. Lekutat;J. Isner
背景血管内皮生长因子（VEGF）/血管通透性因子（VPF）是内皮细胞（EC）有丝分裂原。该特征被认为是VEGF/VPF在促进血管生成中的记录作用的核心。最近的证据表明，VEGF/VPF也可能起到“维持”功能，调节EC生物学的各个方面。在本研究中，我们试图确定在何种程度上VEGF/VPF可以刺激释放NO从正常的EC。方法和结果VEGF/VPF可使兔胸主动脉、肺动脉和下腔静脉血管段的NO浓度（[NO]）呈剂量依赖性升高。与乙酰胆碱刺激相比，VEGF/VPF给药后[NO]增加的开始较慢，在8分钟后达到最大值。用L-精氨酸预孵育主动脉节段使基线[NO]和加入2.5 μ g/mL VEGF/VPF刺激的[NO]均增加两倍。从Krebs溶液中去除CaCl 2，破坏内皮，并给予NG-单甲基-L-精氨酸，消除了10 μ g/mL VEGF/VPF的刺激作用。用一氧化氮特异性极谱电极测量培养的人脐静脉内皮细胞释放的一氧化氮，也记录了类似的结果。结论VEGF/VPF可刺激兔和人内皮细胞产生NO。这一发现（1）构成了成年兔和人EC静止内皮细胞上存在功能性VEGF/VPF受体的推论证据，（2）支持了VEGF/VPF的假定维持功能可能包括调节基线合成和/或EC NO释放的观点。
BACKGROUND Vascular endothelial growth factor (VEGF)/ vascular permeability factor (VPF) is an endothelial cell (EC) mitogen. This feature is considered central to the documented role of VEGF/VPF in promoting angiogenesis. More recent evidence suggests that VEGF/VPF may also serve a "maintenance" function, modulating various aspects of EC biology. In the present study, we sought to determine the extent to which VEGF/VPF may stimulate the release of NO from normal ECs. METHODS AND RESULTS VEGF/VPF produced a dose-dependent rise in NO concentration ([NO]) from vascular segments of rabbit thoracic aorta, pulmonary artery, and inferior vena cava. In comparison to stimulation with acetylcholine, the onset of increased [NO] after administration of VEGF/VPF was slower, reaching a maximum value after 8 minutes. Preincubation of the aortic segments with L-arginine raised by twofold both baseline [NO] and [NO] stimulated by addition of 2.5 micrograms/mL VEGF/VPF. Removal of CaCl2 from the Krebs solution, disruption of the endothelium, and administration of NG-monomethyl-L-arginine abrogated the stimulatory effect of 10 micrograms/mL VEGF/VPF. Similar findings were documented with an NO-specific polarographic electrode to measure NO released from cultured human umbilical vein ECs. CONCLUSIONS VEGF/VPF stimulates production of NO from rabbit and human ECs. This finding (1) constitutes inferential evidence for the presence of functional VEGF/VPF receptors on quiescent endothelium of the adult rabbit as well as human ECs and (2) supports the notion that putative maintenance functions of VEGF/VPF may include regulation of baseline synthesis and/or release of EC NO.