Background. We hypothesized that endothelin-1 (ET-1) is an important m
ediator in renal dysfunction under septic conditions. This study clari
fied the pathophysiologic role of ET-1 in renal function under conditi
ons of surgical stress, especially sepsis. Methods. We investigated th
e correlation between ET-1 levels and renal function and the effect of
anti-ET-1 antibody (AwET-1N40) on renal function in a septic shock ra
t model. Results. The plasma ET-1 level increased significantly at 30
minutes and remained significantly elevated for 24 hours, reaching a p
eak (195 +/- 24.4 pg/ml) 3 hours after the endotoxin (lipopolysacchari
de derived from Escherichia coli) injection. Increases in plasma creat
inine concentration and blood urea nitrogen (BUN) level and decreases
in urine volume and urinary sodium excretion were also observed in the
early phase after endotoxin injection. The plasma creatinine concentr
ation and the plasma ET-1 level increased significantly at 30 minutes,
reached a peak at 3 hours, and then decreased. Anti-ET-1 antibody adm
inistration (5 nmol/kg body, four times intravenously) decreased plasm
a creatinine concentration and BUN level and increased urine volume an
d urinary sodium excretion 3 hours after endotoxin injection (creatini
ne, p = 0.07; BUN, p < 0.05; urine volume, p < 0.01; urinary sodium ex
cretion, p < 0.01; anti-ET-1 vs shams). Conclusions. These results sug
gest that the increase in endogenous ET-1 induced by sepsis plays an i
mportant role in renal dysfunction in the septic state.