Determinants of biliary secretory pressure: the effects of two different bile acids.
Biliary secretory pressure represents the force generated to deliver bile through the biliary system. Bile acid-induced toxicity may decrease canalicular bile formation and (or) induce back diffusion causing cholestasis. To determine if biliary secretory pressure is a sensitive indicator of bile toxicity, taurocholate was compared with a less cytotoxic bile acid, tauroursodeoxycholate. In fasted male Sprague-Dawley rats, the common bile duct was cannulated and the endogenous bile salt pool was removed by enteroclysis. Taurocholate (n = 35) or tauroursodeoxycholate (n = 35) in saline was infused for 1 h. Maximal biliary secretory pressure was then measured by attaching the biliary cannula to a column monometer and recording the maximum height to which bile rose. With taurocholate administration, bile flow and bile salt secretion linearly rose to a maximum infusion of 0.5 mumol/(min.g liver), above which hemolysis and death occurred. In contrast, tauroursodeoxycholate could be infused at higher rates with bile salt secretion plateauing at 1.25 mumol/(min.g liver] Both had similar choleretic potencies. Mean biliary secretory pressure at low (less than 0.15 mumol/(min.g liver] infusions was lower with taurocholate (22.5 cm bile) than tauroursodeoxycholate (25.2 cm). Further, increasing the taurocholate infusion decreased the biliary secretory pressure; yet for taurousodeoxycholate, pressure remained unchanged even at higher infusions. Thus, taurocholate but not tauroursodeoxycholate decreases biliary secretory pressure at high infusion rates, likely a reflection of its toxicity to the hepatobiliary epithelium.
Cole
M J
MJ
Department of Medicine, University of Calgary, Alta, Canada.
Shaffer
E A
EA
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013655:Taurochenodeoxycholic Acid / Q000633:toxicity*; D013656:Taurocholic Acid / Q000633:toxicity*
D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D013655:Taurochenodeoxycholic Acid; D013656:Taurocholic Acid; C031655:ursodoxicoltaurine