Taurolithocholate-induced increase in the intrabiliary pressure generated during retrograde intrabiliary infusion of saline in rats: Antagonism by taurocholate and glycocholate

Taurolithocholate (TLC) is known to produce cholestasis and certain bile acids antagonize this effect. This antagonistic relationship was studied by measuring intrabiliary pressure (IBP) and bile flow changes in pentobarbital-anesthetized male Sprague-Dawley rats weighing 329 ± 7 (SE) g. The IBP reflects the peak pressure generated during the retrograde intrabiliary infusion of saline at 2.3 μl/sec. When TLC was infused into the femoral vein at 0.46 μmol/min over a 35-min period, the IBP rose and the bile flow decreased. Upon stopping the infusion, IBP returned to control values in 30 min but the cholestasis persisted. Simultaneous infusion of taurocholate or glycocholate at 0.61 μmol/min with the TLC prevented the TLC-induced rise in IBP and the cholestasis. Infusion of 0.61 μmol dehydrocholate/min with the TLC did not antagonize the rise in IBP or the cholestasis. Because dehydrocholate was a more potent choleretic agent than taurocholate or glycocholate and it had no antagonistic effect on TLC-induced effects, it was evident that the antagonistic action of taurocholate and glycocholate was not due to their choleretic effect. In another experiment, an iv bolus injection of 100 μmol/kg, taurocholate and glycocholate alone produced a fall in IBP which lasted about 1 hr. Even though this latter kind of fall in IBP might have been consistent with an increase in biliary tree permeability, such an effect did not appear to play a role in the antagonistic effect of these bile salts against the taurolithocholate-induced change. The changes in IBP were likely the result rather than the cause of more fundamental alterations.