Modifications of flow and composition of bile have been studied in the guinea pig with ligated ureters after injection of hypertonic solutions of two nonmetabolizable substances, mannitol and xylose (1.66 m), into the jugular vein. A distinct and persistent decrease in biliary flow always occurs. Analysis of this anticholeresis showed a parallel decrease in the flow of water and electrolytes, while the flow of bilirubin and bile acids is not modified. There are, then, two different types of mechanisms in the formation of bile: the osmotic mechanisms which control the quantity of water and electrolytes; and the active secretory mechanisms, independent of the first, for specific substances such as bilirubin and bile salts. Ultrafiltration does not occur in quantitative formation of bile, but the bile/blood osmotic gradient plays an important role.
Ethacrynic acid (EA) was injected to rats with functional nephrectomy after a control period of steady-state bile flow sustained by taurocholate infusion. Biliary clearance of [14C]mannitol was measured in order to estimate canalicular bile flow and bile salt-independent fraction (BSIF). After EA infusion, bile flow increased by 56%; bile salt excretion rate decreased by 10%; electrolyte excretion rates all increased, principally Na+ and K+. Mannitol clearance increased in parallel with bile flow. The BSIF increased. EA was excreted into bile as a metabolite identified as the cysteine adduct of EA; its excretion rate was linearly correlated with the increment in bile flow. The results are consistent with the hypothesis that the biliary excretion of an EA derivative results in an osmotic water flow increasing the canalicular BSIF. Since EA ia a Na+-K+-ATPase inhibitor, it is necessary to reconsider the relationship between secretion of canalicular BSIF and active Na+ transport mediated by the Na+-K+-ATPase system.
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