title: Effects of chronic hypoxia on renal PDGF-A, PDGF-B, and VEGF gene expression in rats.
abstract: BACKGROUND
  There is evidence from in vitro studies to suggest that the genes of platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) are, like the erythropoietin gene, regulated by oxygen tension. Hypoxia-induced stimulation of, for example, PDGF or VEGF might be involved in the pathogenesis of acute or chronic renal failure and in renal 'inflammatory' diseases (glomerulonephritis, vasculitis, allograft rejection).
  
  
  METHODS
  Male Wistar rats were exposed to chronic normobaric hypoxia (10% O(2), 90% N(2)) for 4 weeks. Additional groups of rats were treated with the endothelin receptor antagonist LU13525 and the NO donor molsidomine. Renal mRNA levels of PDGF-A, PDGF-B, and VEGF were semiquantitated using RNase protection assays.
  
  
  RESULTS
  Renal gene expression of PDGF-A and PDGF-B was neither affected by 2 or 4 weeks of hypoxia nor by concomitant treatment with LU135252 or molsidomine. Chronic hypoxia did also not change VEGF gene expression; however, concomitant treatment with LU135252 increased all VEGF subtypes (188, 164, 120).
  
  
  CONCLUSIONS
  The findings of the present study suggest that renal PDGF and VEGF gene expression in vivo during chronic hypoxia for 2 and 4 weeks is not sensitive to tissue hypoxia in contrast to cell culture experiments. During chronic hypoxia with concomitant blockade of endothelin receptors, all VEGF subtypes were increased, suggesting an inhibitory action of endothelins with regard to renal VEGF gene expression.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, Deutschland.
authors.forename: F
authors.initials: F
authors.lastname: Schweda
authors.forename: F C
authors.initials: FC
authors.lastname: Blumberg
authors.forename: A
authors.initials: A
authors.lastname: Schweda
authors.forename: C
authors.initials: C
authors.lastname: Nabel
authors.forename: S R
authors.initials: SR
authors.lastname: Holmer
authors.forename: G A
authors.initials: GA
authors.lastname: Riegger
authors.forename: M
authors.initials: M
authors.lastname: Pfeifer
authors.forename: B K
authors.initials: BK
authors.lastname: Krämer
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016228:Endothelial Growth Factors / Q000235:genetics*; D065128:Endothelin Receptor Antagonists; D005786:Gene Expression Regulation; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D008981:Molsidomine / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010666:Phenylpropionates / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D065128:Endothelin Receptor Antagonists; D008222:Lymphokines; D020030:Nitric Oxide Donors; D010666:Phenylpropionates; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C075278:platelet-derived growth factor A; C107831:darusentan; D008981:Molsidomine