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
Thomas CoffmanDuke University Medical Center


Kdrkinase insert domain protein receptor
Vegfavascular endothelial growth factor A