Nephrology Dialysis Transplantation, Vol 13, Issue 4 875-885, Copyright © 1998 by Oxford University Press
B Klanke, M Simon, W Rockl, H Weich, H Stolte and H Grone
Background: Vascular endothelial growth factor (VEGF)
or vascular permeability factor (VPF) is a selective mitogen for
endothelial cells; it increases microvascular permeability and has been
shown to relax isolated canine coronary arteries by an
endothelium-dependent mechanism. In many tissues VEGF/VPF is expressed
after an appropriate stimulus, mostly hypoxia. In the kidney VEGF/VPF is
constitutively expressed in glomerular podocytes and epithelia of
collecting duct. Glomerular and peritubular capillary endothelia also
constitutively express specific VEGF receptors. The in
vivo function of renal VEGF/VPF is unknown.
Method: In the present study the effects of human
recombinant VEGF165 on renal haemodynamics and glomerular permselectivity
was investigated in the isolated perfused kidney of the rat.
Results: In kidneys preconstricted by noradrenaline
(NA 1.5x10-7 mol/l) VEGF/VPF (155 pmol/l) caused an
almost complete return of renal perfusion flow rate to preNA values (before
NA 113±4%, after NA 1000%, 15 min with VEGF/VPF
111±4%). Shortly after VEGF/VPF administration VEGF/VPF-induced
relaxation commenced, and became significant after 2 min (15 min with
VEGF/VPF vs without VEGF/VPF 111±4%
vs 103±2%; P<0.05). In the presence
of the NO-synthase inhibitor
NW-nitro-L-arginine
(LNNA; 5x10-5 mol/l) VEGF/VPF
caused only small, transient relaxations (before NNA 109±5%,
after NNA 100%, 15 min with VEGF 95±2%). The cyclooxygenase
inhibitor diclofenac failed to inhibit the relaxing activity of VEGF/VPF
(before NA 119±4%, after NA+diclofenac 100%, 15 min with
VEGF/VPF 123±5%). VEGF demonstrated no significant increase in
renal protein excretion rate (after NA pretreatment (=100%): 12.5 min with
VEGF/VPF vs without VEGF/VPF: 119±10%
vs 132±11%, n.s.) (after NNA pretreatment
(=100%) 12.5 min with VEGF/VPF vs without VEGF/VPF
94±5% vs 96±4%; n.s.) or
clearance quotient of albumin. Glomerular filtration rate was not
influenced by VEGF/VPF in kidneys pretreated with NA (before NA
105±5%, after NA 100%, 12.5 min with VEGF/VPF 94±2%)
or with NNA (before NNA 107±6% after NNA 100%, 12.5 min with
VEGF/VPF 96%±2%). Fractional glucose and fractional sodium
excretion showed flow-dependent changes. Conclusion:
VEGF/VPF can contribute to the relaxing capacity of the renal vasculature.
This relaxation is partly mediated by the NO/endothelium-derived relaxing
factor (EDRF) pathway. In the isolated perfused rat kidney the glomerular
permeability for albumin is not affected by VEGF/VPF. Key
words: vascular endothelial growth factor; vascular permeability
factor; endothelium-dependent vasodilation; endothelium-derived relaxing
factor; glomerular permeability;
NW-nitro-L-arginine
ORIGINAL ARTICLES
Effects of vascular endothelial growth factor (EGF)/vascular permeability factor (VPF) on haemodynamics and permselectivity of the isolated perfused rat kidney
Exp. Nephrology, Department of Nephrology, Medical School Hannover, Hannover, Germany; Department of Pathology, Philipps University of Marburg, Klinikum Lahnberge, D-35043 Marburg, Germany; Department of Gene Expression, Gesellschaft fur Biotechnologische Forschung (GBF), Braunschweig, Germany; Corresponding author
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