Diabetes and radiocontrast media increase endothelin converting enzyme-1 in the kidney.
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.
Khamaisi
M
M
Department of Medicine, Hadassah Hospital, Ein Kerem, The Hebrew University Medical School, Jerusalem, Israel. murir@hadassah.org.il
Raz
I
I
Shilo
V
V
Shina
A
A
Rosenberger
C
C
Dahan
R
R
Abassi
Z
Z
Meidan
R
R
Lecht
S
S
Heyman
S N
SN
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000032:analysis* / Q000235:genetics; D003287:Contrast Media / Q000009:adverse effects*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology*; D003928:Diabetic Nephropathies / Q000209:etiology*; D019332:Endothelin-1 / Q000032:analysis; D000072396:Endothelin-Converting Enzymes; D007668:Kidney / Q000201:enzymology*; D008666:Metalloendopeptidases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D015854:Up-Regulation
D003287:Contrast Media; D019332:Endothelin-1; D012333:RNA, Messenger; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes