Hypoxia and cobalt stimulate vascular endothelial growth factor receptor gene expression in rats

Pflugers Arch. 1997 Apr;433(6):803-8. doi: 10.1007/s004240050348.


This study aimed to examine the influence of acute tissue hypo-oxygenation on the expression of the vascular endothelial growth factor (VEGF) receptor genes. To this end male Sprague-Dawley rats were exposed to different hypoxic conditions such as 10% or 8% oxygen, 0.1% carbon monoxide and cobalt chloride (60 mg/kg) for 6 h and the abundance of flt-1, flt-4 and flk-1 mRNA in lungs and livers was determined by RNase protection assay. The relative proportions of flt-1, flt-4 and flk-1 were 10:2.5:1 and 10:10:2 in normoxic lungs and livers, respectively. It was found that 8% but not 10% oxygen increased flt-1 mRNA two- to three-fold in both organs, whilst flt-4 and flk-1 mRNA were not changed by acute inspiratory hypoxia. Carbon monoxide inhalation also increased flt-1 mRNA but not flt-4 or flk-1 mRNA in both organs. Subcutaneous cobalt administration increased flt-1 mRNA in the livers only, whilst flt-4 and flk-1 mRNA remained unchanged. These findings show that acute tissue hypo-oxygenation is a rather selective stimulus for flt-1 gene expression. The efficiency of the different manoeuvres applied to stimulate flt-1 gene expression is rather similar to the stimulation of erythropoietin gene expression. It is not unreasonable to assume, therefore, that the oxygen-dependent regulation of both genes at the cellular level has significant similarities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Carbon Monoxide / toxicity
  • Cobalt / pharmacology*
  • Glyceraldehyde-3-Phosphate Dehydrogenases / biosynthesis
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Hypoxia / metabolism*
  • Liver / metabolism
  • Lung / metabolism
  • Male
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / isolation & purification
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases / biosynthesis*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptors, Growth Factor / biosynthesis*
  • Receptors, Growth Factor / genetics
  • Receptors, Mitogen / biosynthesis*
  • Receptors, Mitogen / genetics
  • Receptors, Vascular Endothelial Growth Factor
  • Ribonucleases / antagonists & inhibitors
  • Ribonucleases / metabolism
  • Up-Regulation / drug effects*
  • Up-Regulation / physiology


  • RNA, Messenger
  • Receptors, Growth Factor
  • Receptors, Mitogen
  • Cobalt
  • Carbon Monoxide
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • Ribonucleases