PATHOPHYSIOLOGIC ROLE OF ENDOTHELIN-1 IN RENAL-FUNCTION IN RATS WITH ENDOTOXIN-SHOCK

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.