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Blockade Of Endogenous Vascular Endothelial Growth Factor (VEGF) Reveals A Role For Endothelium In The Regulation Of Mammalian Glomerular Permeability
Author(s) -
Salmon Andy,
Bates Dave,
Harper Steve
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a763
Subject(s) - endocrinology , vascular permeability , medicine , renal function , endogeny , chemistry , vascular endothelial growth factor , endothelium , permeability (electromagnetism) , vegf receptors , membrane , biochemistry
Avastin, a monoclonal antibody against VEGF, causes proteinuria and hypertension in some recipients 1 . VEGF is present in normal renal glomeruli 2 , alters glomerular endothelial cell 3 and podocyte 4 behaviour in vitro , but only endothelial cells express VEGF‐receptor2 (VEGF‐R2) 3 , 4 . To determine whether endogenous glomerular VEGF serves to maintain the high resting permeability to water seen in renal glomeruli, isolated intact mammalian glomeruli were exposed to test substance for 60 minutes, and then exposed to a trans‐filtration barrier albumin oncotic gradient within a flow‐controlled observation chamber. Glomerular permeability to water is calculated from the volumetric response (normalised ultrafiltration coefficient: L p A/V i : min −1 .mmHg −1 ; mean fractional filtration rate: J v f: s −1 ) 5Results mean±S.E.M.; Statistics: one‐way ANOVA (Bonferroni) vs control alone. Control (n=41) L p A/V i (0.85±0.05) and J v f magnitude (−0.32±0.01) were reduced by both the pan‐VEGF receptor inhibitor 100nM PTK787 (n=16) (0.69±0.07: p>0.05; −0.26±0.01: p<0.05), and by the selective VEGF‐R2 inhibitor 10nM ZM323881 (n=18) (0.64±0.08: p<0.05; −0.23±0.02: p<0.01). These results indicate that endogenous VEGF contributes to the resting glomerular permeability to water via an action on endothelium. Funding: Wellcome Trust 69134.