Imidapril inhibits increased transforming growth factor-beta1 expression in remnant kidney model.
To elucidate the effect of imidapril, an angiotensin-converting enzyme inhibitor, on molecular events in progressive glomerulosclerosis, we administered imidapril to 5/6 nephrectomized rats and measured the glomerular expression of genes for transforming growth factor (TGF)-beta1, fibronectin and collagen IV. Glomerular TGF-beta1, fibronectin and collagen IV mRNAs in nephrectomized rats were significantly higher than those in sham-operated rats. Treatment with imidapril for 10 weeks significantly reduced the enhanced glomerular expression of TGF-beta1 and collagen IV mRNA in nephrectomized rats, and prevented the associated proteinuria and glomerulosclerosis. Thus, imidapril may arrest progressive glomerulosclerosis by inhibiting the expression of TGF-beta1 and collagen IV.
Hamaguchi
A
A
Department of Pharmacology, Osaka City University Medical School, Osaka, Japan.
Kim
S
S
Wanibuchi
H
H
Iwao
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D011507:Proteinuria / Q000652:urine; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012598:Sclerosis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D005353:Fibronectins; D007093:Imidazoles; D048289:Imidazolidines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; C065166:imidapril