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Sunitha Lakshminarayanan, David A. Antonetti, Thomas W. Gardner, John M. Tarbell; Effect of VEGF on Retinal Microvascular Endothelial Hydraulic Conductivity: The Role of NO. Invest. Ophthalmol. Vis. Sci. 2000;41(13):4256-4261.
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purpose. Vascular endothelial growth factor (VEGF) increases microvascular
permeability in vivo and has been hypothesized to play a role in plasma
leakage in diabetic retinopathy. Few controlled studies have been
conducted to determine the mechanism underlying the effect of VEGF on
transport properties (e.g., hydraulic conductivity [Lp]). This
study was conducted to determine the effect of VEGF on bovine retinal
microvascular endothelial Lp and the role of nitric oxide
(NO) and the guanylate cyclase/guanosine 3′,5′-cyclic
monophosphate/protein kinase G (GC/cGMP/PKG) pathway downstream of NO
in mediating the VEGF response.
methods. Bovine retinal microvascular endothelial cells (BRECs) were grown on
porous polycarbonate filters, and water flux across BREC monolayers in
response to a pressure differential was measured to determine
results. VEGF (100 ng/ml) increased endothelial Lp within 30 minutes
of addition and by 13.8-fold at the end of 3 hours of exposure. VEGF
stimulated endothelial monolayers to release NO and incubation of the
BRECs with the nitric oxide synthase inhibitor N G-monomethyl-l-arginine
(l-NMMA; 100 μM) significantly attenuated the
VEGF-induced Lp increase. It was observed that incubation of
the monolayers with the GC inhibitor LY-83583 (10 μM) did not alter
the VEGF-mediated Lp response. Addition of the cGMP analogue
8-br-cGMP (1 mM) did not change the baseline Lp over 4
hours. Also, the PKG inhibitor KT5823 (1 μM) did not inhibit the
response of BREC Lp to VEGF.
conclusions. These experiments indicate that VEGF elevates hydraulic conductivity in
BRECs through a signaling mechanism that involves NO but not the
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