Comparison of vanadate and ouabain effects on liver hemodynamics and bile production in the perfused rat liver

OO Thomsen and JA Larsen

Cumulative addition of vanadate or ouabain to rat liver perfusions giving perfusate concentrations up to about 500 microM revealed that both liver hemodynamics and bile production are influenced by these substances, but their ways of action differed markedly. Vanadate increased hepatic vascular resistance in a dose-dependent manner with an apparent Km of 30 microM. Not until vanadate concentrations in perfusate reached 60 to 70 microM did the hepatic oxygen consumption decrease significantly together with a decrease in bile flow. Ouabain at perfusate concentrations up to nearly 300 microM caused only a slight fall in perfusate flow, a dose-dependent slight fall in oxygen uptake and a dose-dependent, marked increase in bile flow. Further addition of even small amounts of ouabain initiated a marked fall in perfusate flow, oxygen uptake and bile production and appeared to induce maldistribution of intrahepatic perfusate flow. The vasoconstrictive effect of vanadate was not influenced by alpha or beta blockers, atropine or blockers of Ca++-transport, whereas the effect of ouabain could be strongly reduced by phenoxybenzamine or verapamil. Vanadate-induced vasoconstriction may be caused by an inhibition of smooth muscle Ca++-adenosine triphosphatase and ouabain may induce vasoconstriction by inhibiton of smooth muscle Na, K-adenosine triphosphatase. The hepatic uptake and excretion of ouabain may explain the choleresis observed at small perfusate concentrations of ouabain. Inhibition of bile production at higher concentrations of ouabain and vanadate could be secondary to simultaneous changes in liver hemodynamics.

Volume 221, Issue 1, pp. 197-205, 04/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics