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

摘要

1. We examined the effects of experimental obstructive jaundice caused by bile duct ligation (BDL) on vascular smooth muscle function, as well as the underlying mechanisms involved, by recording responses to noradrenaline (NA), 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) in canine isolated renal arteries and to NA in isolated mesenteric arteries in vitro. All studies 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 attenuated with no change in agonist potency (pD2 value) in renal arteries with 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 KCl could be detected at 7 day BDL. Endothelium-dependent relaxations produced by ACh were significantly increased in renal artery rings from 7 day BDL dogs, but the endothelium-independent relaxations produced by papaverine in BDL preparations were not changed when compared with SO controls. 3. At 7 and 15 days after BDL, the Emax values of the mesenteric ring of BDL dogs to NA were significantly lower than that of SO controls, whereas 3 days after surgery there was no significant difference. The pD2 values in arteries obtained from 15 day BDL animals were significantly lower than those obtained from SO control animals. However, no significant changes in pD2 values were seen 3 and 7 days after the onset of BDL. 4. In conclusion, it is suggested that enhanced production and/or release of nitric oxide, mainly of endothelial origin, is associated with reduced vascular responses to contractile agents in experimental obstructive jaundice and that this effect is related to the duration of obstructive jaundice. These results may explain, at least in part, a cause of hypotension that leads to renal failure in patients with obstructive jaundice.