Effect of vascular endothelial growth factor on nitric oxide production by cultured rat mesangial cells

Biochem Biophys Res Commun. 1998 Apr 17;245(2):443-6. doi: 10.1006/bbrc.1998.8454.

Abstract

Vascular endothelial growth factor (VEGF) stimulates nitric oxide (NO) production by endothelial cells in vitro and in vivo. However, the impact of VEGF on inducible nitric oxide synthase (iNOS) activity and NO synthesis in cultured mesangial cells is not known. Therefore, we measured nitrite accumulation in cytokine-stimulated, rat mesangial cells (RMC) in response to graded concentrations of VEGF. Addition of VEGF (10-50 ng/ml) did not alter RMC viability or NO production in either normal (5.6 mM) or high (33.3 mM) glucose conditions. Exposure of RMC to VEGF did not modify the effects of L-arginine (20 mM) or L-NAME (1 mM) on nitrite accumulation in normal or high glucose media. The steady state abundance of iNOS mRNA and the cytosolic content of iNOS protein were unaffected by addition of VEGF. Cultured RMC expressed the high-affinity tyrosine kinase VEGF receptors, flt and flk/KDR, and the levels were not modulated by incubation in normal or high glucose media. We conclude that VEGF does not regulate proliferation or NO production in cultured RMC. These findings suggest that disturbances in the normal interaction between VEGF and NO are not involved in the pathogenesis of abnormal mesangial cell structure or function in diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Diabetic Neuropathies / physiopathology
  • Endothelial Growth Factors / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Glomerular Mesangium / drug effects*
  • Glucose / pharmacology
  • Lymphokines / pharmacology*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Enzyme Inhibitors
  • Lymphokines
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1
  • Glucose
  • NG-Nitroarginine Methyl Ester