Effects of experimental obstructive jaundice on contractile responses of dog isolated blood vessels: Role of endothelium and duration of bile duct ligation

1. We examined the effects of experimental obstructive jaundice caused by b ile duct ligation (BDL) on vascular smooth muscle function, as well as the underlying mechanisms involved, by recording responses to noradrenaline (NA ), 5-hydroxy-tryptaminc (5-HT) and acetylcholine (ACh) in canine isolated r enal arteries and to NA in Isolated mesenteric arteries in vitro. All studi es were performed 7 days after the onset of BDL in renal arteries and 3, 7 and 15 days after the onset of BDL in mesenteric arteries. 2. The maximum contraction evoked by both NA and 5-HT was significantly att enuated with no change in agonist potency (pD(2) value) in renal arteries w ith endothelium obtained from 7 day BDL dogs when compared with those from sham-operated controls (SO). However, the reduction almost disappeared when the endothelium was removed. In contrast, no change in the responsiveness of renal arteries to KCI could be detected at 7 day BDL. Endothelium-depend ent relaxations produced by ACh were significantly increased in renal arter y rings from 7 day BDL dogs, but the endothelium-independent relaxations pr oduced by papaverine in BDL preparations were not changed when compared wit h SO controls. 3. At 7 and 15 days after BDL, the E-max values of the mesenteric ring of B DL dogs to NA were significantly lower than that of SO controls, whereas 3 days after surgery there was no significant difference. The pD(2) values in arteries obtained from 15 day BDL, animals were significantly Lower than t hose obtained from SO control animals. However, no significant changes in p ot values were seen 3 and 7 days after the onset of BDL. 4. In conclusion, it is suggested that enhanced production and/or release o f nitric oxide, mainly of endothelial origin, is associated with reduced va scular responses to contractile agents in experimental obstructive jaundice and that this effect is related to the duration of obstructive jaundice. T hese results may explain, at least in part, a cause of hypotension that lea ds to renal failure in patients with obstructive jaundice.