Increased renal glomerular endothelin-1 release in gentamicin-induced nephrotoxicity

Gentamicin-induced acute renal failure is characterized by a decrease in re nal 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 ge ntamicin-induced renal failure. Renal glomerular release of ET-1 was measur ed 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-16 40. Glomerular supernatant and plasma concentration of ET-1 were measured b y RIA. Renal failure was assessed by insulin, para-aminohippuric and creati nine clearance and histological studies. Gentamicin induced a dose number-d ependent increase in plasma creatinine and a decrease in creatinine clearan ce. This was accompanied by a marked decrease in inulin and para-aminohippu ric acid clearance, as well as by a marked tubular necrosis, without altera tions in glomerular structures. Plasma ET-1 concentration and glomerular ET -1 release were also increased in gentamicin-treated rats. When 10(-5) M ge ntamicin 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 e levated ET-1 plasma levels and increased glomerular release of ET-1 could m ediate, at least in part, the decrease in glomerular filtration rate observ ed in gentamicin-induced ARF.