IMPAIRED RENAL-FUNCTION IN OBSTRUCTIVE-JAUNDICE - ROLES OF THE THROMBOXANE AND ENDOTHELIN SYSTEMS

Patients with intra-or extrahepatic bile-duct obstruction are suscepti ble to acute renal failure (ARF) especially when undergoing major surg ery. We observed in jaundiced rats 4 days after bile-duct ligation (BD L) a decrease in GFR accompanied by polyuria which is associated with increased urinary thromboxane (TX) excretion and glomerular TXB2 synth esis. The TXA(2)/PGH(2) receptor antagonist daltroban normalized GFR b ut not urine concentration. There was also a rise in plasma and urinar y endothelin (ET-1) with increased papillary ET synthesis. The ETA/ETB receptor blocker bosentan restored GFR and the renal concentrating ab ility. Since we showed previously that ET-induced decreases in renal p erfusion and ultrafiltration coefficient K-f are mediated by other aut acoids such as TX, this may explain why both bosentan and daltroban no rmalized GFR. These results suggest that increased renal glomerular TX and vascular and inner medullary collecting duct ET synthesis contrib ute to defective GFR and distal tubular function in experimental BDL. Similar alterations may also predispose the human kidney to ARF in pat ients with obstructive jaundice.