Vascular endothelial growth factor increases the ultrafiltration coefficient in isolated intact Wistar rat glomeruli.
Vascular endothelial growth factor (VEGF) is expressed by the podocytes of renal glomeruli, and has profound influences on systemic microvascular permeability and haemodynamics. We describe an extensive refinement of a model that permits evaluation of the ultrafiltration coefficient (LpA) of isolated mammalian glomeruli, in the absence of circulating and haemodynamic influences, and tested the hypothesis that VEGF influences glomerular LpA via an effect on endothelial cells. Glomeruli were isolated by sieving Wistar rat renal cortical tissue, and individually loaded onto a suction micropipette. Flowing perifusate containing 1% bovine serum albumin (BSA) was rapidly switched to an oncopressive perifusate containing 8% BSA, eliciting transglomerular fluid efflux. The rate of the resultant reduction in glomerular volume was used to calculate glomerular LpA (1.07 +/- 0.53 nl min(-1) mmHg(-1) (mean +/-s.d.), n= 51), which compares favourably with those reported in the same rat strain using different techniques. A significant relationship between LpA and initial glomerular volume (Vi) (r= 0.72, n= 41, P < 0.0001) necessitated correction of LpA for Vi. The initial rate of change of glomerular volume, normalized for Vi, showed a strong positive correlation with applied oncotic gradient (Pearson r= 0.59, n= 28, P < 0.001), as predicted by Starling's law of filtration. A 60 min exposure of glomeruli to 1 nm VEGF increased glomerular LpA/Vi (1.19 +/- 0.19 (n= 10) to 2.23 +/- 0.33 (n= 9) min(-1) mmHg(-1) (mean +/-s.e.m.); P < 0.02). Time- and concentration-dependent relations between VEGF and LpA/Vi were observed. The VEGF-induced elevation of LpA/Vi was blocked by the selective VEGF-R2 inhibitor ZM323881. We suggest that glomerular VEGF contributes to the high physiological permeability of mammalian glomeruli to water through an action on endothelial cells.
Salmon
Andrew H J
AH
Microvascular Research Laboratories, Department of Physiology, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK.
Neal
Christopher R
CR
Bates
David O
DO
Harper
Steven J
SJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010539:Permeability; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects; D014867:Water / Q000378:metabolism
D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; C478783:ZM323881; D014867:Water; D040301:Vascular Endothelial Growth Factor Receptor-2