Abstract
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 μg/mL VEGF/VPF. Removal of CaCl 2 from the Krebs solution, disruption of the endothelium, and administration of N G -monomethyl- l -arginine abrogated the stimulatory effect of 10 μg/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.
References
48
Referenced
289
10.1172/JCI116092
- Rubanyi GM, Romero JC, Vanhoutte PM. Flow induced release of endothelium-derived relaxing factor. Am J Physiol. 1986;250:41145-41149. / Am J Physiol (1986)
10.1161/res.70.1.1345777
10.1161/01.hyp.8.1.37
10.1161/res.73.2.7687202
10.1126/science.2479987
10.1126/science.2479986
10.1002/j.1460-2075.1989.tb08557.x
10.1073/pnas.90.19.8915
10.1172/JCI115568
10.1038/nm1095-1024
- Shifren JL, Doldi N, Ferrara N, Mesiano S, Jaffe RB. In the human fetus, vascular endothelial growth factor is expressed in epithelial cells and myocytes, but not vascular endothelium: implications for mode of action. J Clin Endocrinol Metab. 1994;79:316-322. / J Clin Endocrinol Metab (1994)
- Brock TA, Dvorak HF, Senger DR. Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. Am J Pathol. 1991;138:213-221. / Am J Pathol (1991)
10.1152/ajpheart.1993.265.2.H586
10.1161/circ.91.11.2802
- Horowitz J Hariawala M Sheriff DD Keyt B Symes JF. In vivo administration of vascular endothelial growth factor is associated with EDRF-dependent systemic hypotension in porcine and rabbit animal models. Circulation. 1995;92(suppl I):I-630-I-631. Abstract.
10.1161/circ.91.11.2793
10.1016/0735-1097(95)00439-4
10.1073/pnas.89.23.11259
10.1073/pnas.84.24.9265
- Callow AD. What's new in endothelial cell biology and its clinical relevance? Curr Crit Prob Vasc Surg. 1994;10:71-74. / Curr Crit Prob Vasc Surg (1994)
- Shibuki K, Okada D. Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum. Nature. 1991;358:676-678. / Nature (1991)
10.1161/res.75.4.7923615
- Walter DH, Hink U, Asahara T, Van Belle E, Horowitz J, Tsurumi Y, Vandlen R, Heinsohn H, Keyt B, Ferrara N, Symes JF, Isner JM. The in vivo bioactivity of vascular endothelial growth factor/vascular permeability factor is independent of N-linked glycosylation. Lab Invest. 1996;74:546-556. / Lab Invest (1996)
10.1093/ajcp/100.5.567
10.1126/science.1281928
10.1006/abio.1993.1449
10.1002/jcp.1041360107
10.1126/science.1312256
10.1016/0092-8674(93)90573-9
- Gao Y, Zhou H, Raj JU. Heterogeneity in role of endothelium-derived NO in pulmonary arteries and veins of full-term fetal lambs. Am J Physiol. 1995;268:H1586-H1592. / Am J Physiol (1995)
- Steinhorn RH, Morin FC III, Gugino SF, Giese EC, Russel JA. Developmental differences in endothelium-dependent responses in isolated ovine pulmonary arteries and veins. Am J Physiol. 1993;33:H2162-H2167. / Am J Physiol (1993)
- Miller VM. Selective production of endothelium-derived nitric oxide in canine femoral veins. Am J Physiol. 1991;261:H677-H682. / Am J Physiol (1991)
10.1111/j.1476-5381.1987.tb11369.x
10.1084/jem.180.3.1141
10.1016/0046-8177(95)90119-1
10.1002/ijc.2910590415
10.1172/JCI118437
10.1172/JCI117858
10.1172/JCI114081
- Scott-Burden T Vanhoutte PM. The endothelium as a regulator of vascular smooth muscle proliferation. Circulation. 1993;87(suppl V):V-51-V-58.
10.1097/00005344-199508000-00013
10.1073/pnas.92.4.1137
10.1172/JCI118328
10.1126/science.2432664
10.1146/annurev.ph.49.030187.002321
10.1073/pnas.91.10.4190
- Asahara T, Bauters C, Wu T, Zheng LP, Chen D, Symes J, Isner JM. Nitric oxide precursor augments angiogenesis and attenuates endothelial dysfunction in collateral circulation in rabbit ischemic hindlimb in vivo. FASEB J. 1996;10:A545. Abstract. / FASEB J (1996)
Dates
Type | When |
---|---|
Created | 13 years, 2 months ago (June 11, 2012, 8:41 p.m.) |
Deposited | 1 year, 3 months ago (May 12, 2024, 12:54 p.m.) |
Indexed | 2 weeks ago (Aug. 23, 2025, 1:08 a.m.) |
Issued | 28 years, 6 months ago (Feb. 18, 1997) |
Published | 28 years, 6 months ago (Feb. 18, 1997) |
Published Print | 28 years, 6 months ago (Feb. 18, 1997) |
@article{van_der_Zee_1997, title={Vascular Endothelial Growth Factor/Vascular Permeability Factor Augments Nitric Oxide Release From Quiescent Rabbit and Human Vascular Endothelium}, volume={95}, ISSN={1524-4539}, url={http://dx.doi.org/10.1161/01.cir.95.4.1030}, DOI={10.1161/01.cir.95.4.1030}, number={4}, journal={Circulation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={van der Zee, Rien and Murohara, Toyoaki and Luo, Zhengyu and Zollmann, Frank and Passeri, Jonathan and Lekutat, Carsten and Isner, Jeffrey M.}, year={1997}, month=feb, pages={1030–1037} }