Pathophysiologic role of endothelin-1 in renal function in rats with endotoxin shock

We hypothesized that endothelin-1 (ET-1) is an important mediator in renal dysfunction under septic conditions. This study clarified the pathophysiologic role of ET-1 in renal function under conditions of surgical stress, especially sepsis.

We investigated the 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 rat model.

The plasma ET-1 level increased significantly at 30 minutes and remained significantly elevated for 24 hours, reaching a peak (195 +/- 24.4 pg/ml) 3 hours after the endotoxin (lipopolysaccharide derived from Escherichia coli) injection. Increases in plasma creatinine 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 concentration and the plasma ET-1 level increased significantly at 30 minutes, reached a peak at 3 hours, and then decreased. Anti-ET-1 antibody administration (5 nmol/kg body, four times intravenously) decreased plasma creatinine concentration and BUN level and increased urine volume and urinary sodium excretion 3 hours after endotoxin injection (creatinine, p = 0.07; BUN, p < 0.05; urine volume, p < 0.01; urinary sodium excretion, p < 0.01; anti-ET-1 vs shams).

These results suggest that the increase in endogenous ET-1 induced by sepsis plays an important role in renal dysfunction in the septic state.