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Publication
Vascular endothelial growth factor receptor 2 controls blood pressure by
regulating nitric oxide synthase expression.
Authors
Facemire CS, Nixon AB, Griffiths R, Hurwitz H, Coffman TM
Submitted By
Thomas Coffman on 3/24/2010
Status
Published
Journal
Hypertension
Year
2009
Date Published
9/1/2009
Volume : Pages
54(3) : 652 - 658
PubMed Reference
19652084
Abstract
Drugs and antibodies that interrupt vascular endothelial growth factor (VEGF)
signaling pathways improve outcomes in patients with a variety of cancers by
inhibiting tumor angiogenesis. A major adverse effect of these treatments is
hypertension, suggesting a critical role for VEGF in blood pressure (BP)
regulation. However, the physiological mechanisms underlying the control of BP
by VEGF are unclear. To address this question, we administered a specific
antibody against the major VEGF receptor, VEGFR2, to normal mice and assessed
the consequences on BP. Compared with vehicle-treated controls, administration
of the anti-VEGFR2 antibody caused a rapid and sustained increase in BP of
approximately 10 mm Hg. This increase in BP was associated with a significant
reduction in renin mRNA expression in the kidney (P=0.019) and in urinary
excretion of aldosterone (P<0.05). Treatment with the anti-VEGFR2 antibody also
caused a marked reduction in the expression of endothelial and neuronal NO
synthases in the kidney. To examine the role of NO in the hypertension caused by
blocking VEGFR2, mice were treated with N(omega)-nitro-L-arginine methyl ester
(L-NAME) (20 mg/kg per day), an inhibitor of NO production. L-NAME
administration abolished the difference in BP between the vehicle- and
anti-VEGFR2-treated groups. Our data suggest that VEGF, acting via VEGFR2, plays
a critical role in BP control by promoting NO synthase expression and NO
activity. Interfering with this pathway is likely to be one mechanism underlying
hypertension caused by antiangiogenic agents targeting VEGF.
Investigators with authorship
Name
Institution
Thomas Coffman
Duke University Medical Center
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Genes
Symbol
Description
Kdr
kinase insert domain protein receptor
Vegfa
vascular endothelial growth factor A
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Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
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