title: Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium.
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.
  
  
  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.
authors.affiliation: Department of Biomedical Research, St Elizabeth's Medical Center, Tufts University, School of Medicine, Boston, Mass 02135-2997, USA.
authors.forename: R
authors.initials: R
authors.lastname: van der Zee
authors.forename: T
authors.initials: T
authors.lastname: Murohara
authors.forename: Z
authors.initials: Z
authors.lastname: Luo
authors.forename: F
authors.initials: F
authors.lastname: Zollmann
authors.forename: J
authors.initials: J
authors.lastname: Passeri
authors.forename: C
authors.initials: C
authors.lastname: Lekutat
authors.forename: J M
authors.initials: JM
authors.lastname: Isner
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D001120:Arginine / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000378:metabolism*; D011048:Polarography; D011651:Pulmonary Artery; D011817:Rabbits; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014682:Vena Cava, Inferior; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D002122:Calcium Chloride; D000109:Acetylcholine