Reversible suppression of the vascular contractile response in rats with obstructive jaundice

Both patients and experimental animals with obstructive jaundice manifest vascular instability, with animals showing a blunted vascular response to norepinephrine (NE). We sought an intrinsic abnormality of vascular smooth muscle by studying the contractile response of isolated, helically cut aortic strips and intact portal veins to cumulative doses of NE in rats with bile duct ligation (BDL) at different times compared with sham-operated (SO) rats as controls. At 3 days after surgery, the mean cumulative maximal contractile response (Rmax) of the aortic strip of BDL rats (94.3 +/- 9.0 mg/mg tissue) was significantly lower than that of SO controls (145.3 +/- 11.5 mg/mg tissue) (P less than 0.005), associated with a tendency toward decreased sensitivity (half-maximal dose [ED50]) (18.2 +/- 6.75 nmol/L vs. 6.7 +/- 0.6 nmol/L). By 6 days, there was no difference between the two groups. Similarly, by 3 days the mean Rmax for portal vein contraction in BDL rats (694 +/- 72 mg) was significantly lower than that for SO rats (1000 +/- 143 mg). In contrast, mean ED50 of the portal veins of BDL rats (327 +/- 65 nmol/L) was significantly less than that of SO rats (881 +/- 216 nmol/L), indicating greater sensitivity. At 1 and 6 days after surgery there was no significant difference between the two groups. These alterations in the vascular contractile response coincided with the maximum increases in serum bilirubin and liver enzyme levels. In conclusion, this study indicates that the circulatory abnormalities associated with obstructive jaundice are associated, at least in part, with suppression of the vascular contractile response caused by some abnormality of the vascular musculature.