Increased renal glomerular endothelin-1 release in gentamicin-induced nephrotoxicity.
Gentamicin-induced acute renal failure is characterized by a decrease in renal plasma flow and creatinine clearance. Endothelins (ET) are potent renal vasoconstrictors. The aim of this work is to assess the role of ET-1 in gentamicin-induced renal failure. Renal glomerular release of ET-1 was measured in rats with gentamicin-induced nephrotoxicity (100 mg/kg/day, s.c. for 2, 4 or 6 days). Glomeruli were isolated and incubated for 24 h in RPMI-1640. Glomerular supernatant and plasma concentration of ET-1 were measured by RIA. Renal failure was assessed by insulin, para-aminohippuric and creatinine clearance and histological studies. Gentamicin induced a dose number-dependent increase in plasma creatinine and a decrease in creatinine clearance. This was accompanied by a marked decrease in inulin and para-aminohippuric acid clearance, as well as by a marked tubular necrosis, without alterations in glomerular structures. Plasma ET-1 concentration and glomerular ET-1 release were also increased in gentamicin-treated rats. When 10-5 M gentamicin was added to control glomeruli, ET-1 production was not modified (36.4 +/- 2.2 vs. 35.2 +/- 1.7 pg/ml/24 h). All these results suggest that elevated ET-1 plasma levels and increased glomerular release of ET-1 could mediate, at least in part, the decrease in glomerular filtration rate observed in gentamicin-induced ARF.
Valdivielso
J M
JM
Instituto Reina Sofía de Investigación Nefrológica. Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain.
Rivas-Cabañero
L
L
Morales
A I
AI
Arévalo
M
M
López-Novoa
J M
JM
Pérez-Barriocanal
F
F
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D046508:Culture Techniques; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D005839:Gentamicins / Q000009:adverse effects*; D007668:Kidney / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000378:metabolism*; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar
D019332:Endothelin-1; D005839:Gentamicins; D003404:Creatinine