Effects of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) on haemodynamics and permselectivity of the isolated perfused rat kidney

Nephrol Dial Transplant. 1998 Apr;13(4):875-85. doi: 10.1093/ndt/13.4.875.

Abstract

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 1.5 x 10(-7) mol/l) VEGF/VPF (155 pmol/l) caused an almost complete return of renal perfusion flow rate to pre-NA values (before NA 113 +/- 4%, after NA 100%, 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 N(W)-nitro-L-arginine (L-NNA; 5 x 10(-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endothelial Growth Factors / pharmacology*
  • Hemodynamics / drug effects*
  • Humans
  • Kidney / drug effects*
  • Kidney / physiology
  • Lymphokines / pharmacology*
  • Male
  • Oxygen Consumption / drug effects
  • Perfusion
  • Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Sodium / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Proteins
  • Recombinant Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Sodium