The effects of prostacyclin on canine hepatic bile flow.

Abstract

The effect of prostacyclin on canine hepatic bile flow was evaluated. Utilizing chronic, unanesthetized bile fistula dogs, prostacyclin was found to significantly increase bile flow rates and bile bicarbonate and cyclic AMP concentration and output when compared to control values. The choleretic response was not due to the effect of the principal metabolic endproduct of prostacyclin, 6-keto-PGF1 alpha, as this substance increased bile flow but did not increase bicarbonate or cyclic AMP concentrations in bile. Prostacyclin did not increase [14C]erythritol clearance in bile suggesting that it stimulates bile duct secretion rather than the bile salt-independent fraction of canalicular bile. To ascertain if a relationship exists between the bicarbonate-rich choleresis produced by prostacyclin and that produced by secretin, the effects of prostacyclin and indomethacin on the choleresis produced by endogenous secretin stimulation were evaluated. During intraduodenal acid infusion, prostacyclin significantly increased bile flow. The increase was not secondary to increased secretin release as plasma secretin levels were not significantly changed from control levels. Prostaglandin synthetase inhibition by indomethacin administration did not alter the choleresis produced by intraduodenal acid. The prostacyclin-induced changes in bile flow were further evaluated in acute experiments in anesthetized dogs during which the effects of prostacyclin on systemic blood pressure, hepatic blood flow and cyclic AMP metabolism could be simultaneously determined. The choleresis produced by prostacyclin occurred in the presence of decreased systemic arterial blood pressure and hepatic blood flow. The increased bile cyclic AMP secretion produced by prostacyclin was not associated with increases in systemic or hepatogenous cyclic AMP. Prostacyclin increases canine bile flow and bicarbonate secretion, a process which may be mediated by cyclic AMP. The choleresis is not secondary to changes in hepatic blood flow or secretin release.