The Effect Of Endothelin Receptor Antagonist PD142893 On Renal Function Impairment Of Rats With Obstructive Jaundice

Objective To study the effect of the changes of endothelin(ET) in plasma and kidney tissue of wistar rats with obstructive jaundice(OJ) on renal function and investigate the effect whether change or not after application of endothelin receptor antagonist PD142893. Methods By using specific radioimmunological method ,the levels of plasma ET and kidney ET were measured in rats with common bile duct ligation (OJ group)(n=32) ,those with common bile ligation and application PD142893(OJ+D group) (n=32) and those with sham operation (S group)(n=32) for 5,10,15 and 20 days after operation .Meanwhile the level of serum total bilirubin(TB) and creatinine clearance rate (Ccr)were also determined in all rats. Renal histological changes were observed with optical microscopy . Result The levels of ET in plasma and renal tissue as well as those of serum TB in all OJ rats were continually elevated. The levels of ET in plasma and kidney were closely related to serum TB. Ccr was negativecorrelation with the levels of ET in groups untreated PD142893. Ccr descended on 5day in OJ group and this trendency and changes of pathology were more and more obvious with time. However, the same changes occurred later in OJ+D group. Conclusions Hyperbilirubinemia might be one of the causes leading to renal function impairment(RFI) . Porphobilin might be direct virulence to renal tissue. Various biological effects mediated by ET which were increased in OJ might be most important causes leading to RFI. Endothelin receptor antagonist might have protective effects to RFI in OJ.