Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium.
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.
van der Zee
R
R
Department of Biomedical Research, St Elizabeth's Medical Center, Tufts University, School of Medicine, Boston, Mass 02135-2997, USA.
Murohara
T
T
Luo
Z
Z
Zollmann
F
F
Passeri
J
J
Lekutat
C
C
Isner
J M
JM
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
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