Diabetes and radiocontrast media increase endothelin converting enzyme-1 in the kidney

M. Khamaisi*, I. Raz, V. Shilo, A. Shina, C. Rosenberger, R. Dahan, Z. Abassi, R. Meidan, S. Lecht, S. N. Heyman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Plasma endothelin-1 levels rise in diabetes and after exposure to contrast media suggesting a role in progressive diabetic and acute radiocontrast nephropathies. Here we studied individual and combined effects of streptozotocin-induced diabetes and contrast media on renal endothelin converting enzyme-1 levels in the rat. In vivo, medullary (but not cortical) endothelin converting enzyme protein gradually increased 4 to 5-fold following the induction of diabetes or after the administration of contrast media but rose 15-fold when diabetic rats were given contrast media. Changes in mRNA expression paralleled those of the protein. Immunohistochemistry confirmed that increased tubular and endothelial cell endothelin converting enzyme-1 were most pronounced in the medulla. In vitro, endothelin-1 levels increased 3-fold following incubation of endothelial cells with media high in glucose or with contrast and 4-fold with their combination. Endothelin converting enzyme-1 protein and mRNA expression changed in a similar pattern while prepro endothelin-1 mRNA increased with each insult but not in an additive way. Our study shows that diabetes and contrast media up-regulate renal medullary endothelin converting enzyme-1 expression and synthesis.

Original languageEnglish
Pages (from-to)91-100
Number of pages10
JournalKidney International
Volume74
Issue number1
DOIs
StatePublished - Jul 2008

Keywords

  • Contrast media
  • Diabetes
  • Hypoxia
  • Kidney
  • Rat

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