Role of endotoxin and nitric oxide in the pathogenesis of renal failure in obstructive jaundice.

Abstract

There is an increased incidence of postoperative renal failure in patients with obstructive jaundice. The purpose of this study was to investigate the role of endotoxaemia and nitric oxide in this association. In bile duct-ligated, sham-operated and control rats, plasma total bilirubin levels, creatinine clearance and plasma endotoxin were determined. Endothelium-dependent vasodilatation to acetylcholine, and endothelium-independent vasodilatation to nitroglycerine and forskolin were evaluated in isolated perfused rat kidney. Twenty-one of 27 bile-duct ligated rats had endotoxaemia. Plasma bilirubin levels were higher and creatinine clearance was significantly reduced in the bile duct-ligated endotoxin-positive group compared with values in the other groups. Furthermore, in the isolated perfused rat kidney from rats with endotoxaemia, basal perfusion pressure and renal vascular relaxation to acetylcholine and nitroglycerine which is mediated by guanosine cyclic 3',5'-cyclic monophosphate (cGMP) were significantly reduced, but relaxation to forskolin mediated by adenosine cyclic 3',5'-cyclic monophosphate did not change. Endotoxaemia in obstructive jaundice may induce overproduction of nitric oxide that may lead to impairment of cGMP-associated vasodilatation and disrupt autoregulation of the renal vascular bed. This may contribute to renal failure in obstructive jaundice.