Rapid communication. Enalapril decreases nuclear factor kappa B activation in the kidney with ureteral obstruction.
The transcription factor nuclear factor kappa B (NF-kappa B) controls a number of genes associated with tissue inflammation and has been shown to be activated in the kidney with ureteral obstruction. In this investigation, we further explored NF-kappa B activation in the kidney cortex of rats with unilateral ureteral obstruction. Electrophoretic mobility shift assays combined with antibody supershift/depletion demonstrated that NF-kappa B subunits p50, p52, c-rel, p65 (RelA) and RelB were all activated. Immunocytochemical analysis using an antibody to the p50 subunit demonstrated activation occurring predominantly in nuclei of tubular cells. Treatment of animals with unilateral ureteral obstruction with an oral ACE inhibitor significantly decreased NF-kappa B activation. This suggests that the antiinflammatory effect of ACE inhibitors in renal disease is in part due to a blunting of NF-kappa B activation.
Morrissey
J J
JJ
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Klahr
S
S
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004656:Enalapril / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014517:Ureteral Obstruction / Q000201:enzymology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016328:NF-kappa B; D004656:Enalapril