Effect of the antiglucocorticoid RU-486 on glomerular hemodynamics in remnant nephrons.
Endogenous glucocorticoid (GC) has been proposed to play a role in the adaptive functions of remnant nephron and participates in the progression of renal disease. The effect of GC blockade by RU-486 (20 mg/kg), an anti-GC agent, on the progression of chronic renal failure (CRF) was evaluated in Munich-Wistar rats. CRF was induced by 5/6 nephrectomy. Global renal function, glomerular hemodynamics, proteinuria and renal histopathology studies were performed after 60 days of CRF induction. RU administration in control or CRF groups did not induce significant changes in total renal function, mean arterial or intraglomerular hydraulic pressures, 24-hour proteinuria or sclerosis index. However, RU induced a significant reduction in single-nephron glomerular filtration rate in the superficial nephrons in both groups' control (decreases 20%) and CRF (decreases 57%), without changing total glomerular filtration rate, when compared with vehicle administration. These reductions were due to a decline in glomerular plasma flow rate (QA) and in glomerular ultrafiltration coefficient (Kf). These data suggest that GC played a role in the adaptive hyperfiltration associated with the compensatory mechanism but did not participate in the genesis of proteinuria or glomerulosclerosis in this experimental model.
Cardoso
L R
LR
Nephrology Division, Escola Paulista de Medicina, São Paulo, Brazil.
Oliveira
A V
AV
Santos
O F
OF
Boim
M A
MA
Razvickas
C V
CV
Ajzen
H
H
Schor
N
N
D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000187:drug effects* / Q000502:physiology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D009392:Nephrectomy; D009399:Nephrons / Q000098:blood supply* / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone