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This Article Full Text Full Text (PDF) All Versions of this Article: 570/1/141    most recent jphysiol.2005.099184v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Salmon, A. H. J. Articles by Harper, S. J. Search for Related Content PubMed PubMed Citation Articles by Salmon, A. H. J. Articles by Harper, S. J. Related Collections Renal and Endocrine

¹ Microvascular Research Laboratories, Department of Physiology, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK

Abstract

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 (L_pA) of isolated mammalian glomeruli, in the absence of circulating and haemodynamic influences, and tested the hypothesis that VEGF influences glomerular L_pA 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 L_pA (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 L_pA and initial glomerular volume (V_i) (r= 0.72, n= 41, P < 0.0001) necessitated correction of L_pA for V_i. The initial rate of change of glomerular volume, normalized for V_i, 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 L_pA/V_i (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 L_pA/V_i were observed. The VEGF-induced elevation of L_pA/V_i 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.

(Received 22 September 2005; accepted after revision 19 October 2005; first published online 20 October 2005)
Corresponding author D. O. Bates: Microvascular Research Laboratories, Department of Physiology, School of Veterinary Sciences, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK. Email: dave.bates{at}bristol.ac.uk

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