Cholestasis and changes in the microcirculation of perfused rat liver caused by the calcium ionophore A23187 and type I antiarrhythmic drugs.
The calcium-ionophore A23187 causes a reversible increase of the hydrostatic pressure in the portal vein of perfused rat liver. Concomitantly, hepatic functions like the production of bile and the transhepatic movement of the bile acid taurocholate are diminished, mainly due to decreased uptake. These phenomena are partly explained by changes in the microcirculation of the liver, visualized by Trypan blue staining. Both the increase in portal pressure and the major part of the decrease of biliary excretion of taurocholate and bile flow are prevented by the addition of the vasodilator papaverine. The type I antiarrhythmic drugs quinidine and N-propylajmaline bitartrate (NPA), at high concentrations, also induce a rise in portal pressure and act as a cholestatic agent. The rise in portal pressure caused by NPA requires the presence of extracellular calcium and is counteracted by papaverine. In contrast to A23187, the cholestasis caused by NPA is not influenced by papaverine. While NPA decreases the hepatic uptake and biliary excretion of taurocholate, papavarine is able to restore only the uptake and not the excretion. The concentration of taurocholate in the bile is not significantly changed by NPA.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001646:Bile / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology*; D002779:Cholestasis / Q000139:chemically induced* / Q000503:physiopathology; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D010208:Papaverine / Q000494:pharmacology; D011219:Prajmaline / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D000001:Calcimycin; D013656:Taurocholic Acid; D011219:Prajmaline; D010208:Papaverine; D011802:Quinidine