In:
The Journal of Physiology, Wiley, Vol. 570, No. 1 ( 2006-01), p. 141-156
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 p A ) of isolated mammalian glomeruli, in the absence of circulating and haemodynamic influences, and tested the hypothesis that VEGF influences glomerular L p A 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 p A (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 p A and initial glomerular volume ( V i ) ( r = 0.72, n = 41, P 〈 0.0001) necessitated correction of L p A 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 n m VEGF increased glomerular L p A / 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 p A / V i were observed. The VEGF‐induced elevation of L p A / 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.
Type of Medium:
Online Resource
ISSN:
0022-3751
,
1469-7793
DOI:
10.1113/jphysiol.2005.099184
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
1475290-6
SSG:
12
Permalink