Urinary transforming growth factor-beta (TGF-beta) excretion and renal production of TGF-beta in rats with subtotal renal ablation: effect of enalapril and nifedipine.
The aim of the present study was to investigate the effect of enalapril and nifedipine on renal transforming growth factor-beta (TGF-beta) production and on the rate of urinary TGF-beta excretion in rats with subtotal renal ablation. After subtotal nephrectomy some animals were treated with enalapril or nifedipine. Renal cortical TGF-beta mRNA levels were 68% higher in untreated nephrectomized rats (p < 0.05) and 39% higher in rats treated with nifedipine (p < 0.05) compared with controls. There was no difference in renal cortical TGF-beta mRNA content between the nephrectomized rats treated with enalapril and sham animals, showing that enalapril treatment prevented the increase of TGF-beta mRNA in nephrectomized rats. The rate of urinary TGF-beta excretion was 2.2 +/- 0.8 pg/min in sham animals, 61.5 +/- 40.1 pg/min in untreated nephrectomized rats, 9.6 +/- 4.2 pg/min in nephrectomized rats treated with enalapril, and 55.2 +/- 24.46 pg/min in rats treated with nifedipine. The immunohistochemical reaction for TGF-beta in the renal cortex was less intense in the nephrectomized rats treated with enalapril than in the other groups of rats with subtotal renal ablation. These data show that enalapril induces a decrease in renal TGF-beta production and in urinary TGF-beta excretion in rats with subtotal renal ablation, an effect associated with the protective action of this treatment on renal structure and function and suggest that the determination of the rate of urinary TGF-beta could be a useful procedure for the evaluation of disease progression and therapeutic efficacy in the remnant kidney model.
Monteiro de Freitas
A S
AS
Department of Physiology, Internal Medicine, Medical School of Ribeirão Prêto, University of São Paulo, Brazil.
Coimbra
T M
TM
Costa
R S
RS
Baroni
E A
EA
D000419:Albuminuria / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018450:Disease Progression; D004656:Enalapril / Q000494:pharmacology*; D005923:Glomerulosclerosis, Focal Segmental / Q000503:physiopathology / Q000652:urine*; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000378:metabolism* / Q000503:physiopathology; D008853:Microscopy; D009392:Nephrectomy; D009543:Nifedipine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000652:urine*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004656:Enalapril; D009543:Nifedipine