The heterogeneous response of the bivascularly perfused rat liver to adenosine

Abstract

The heterogeneity of the liver parenchyma in relation to the metabolic response to adenosine was investigated using the bivascularly perfused rat liver in the anterograde and retrograde modes. Adenosine was infused into livers from fed rats according to four experimental protocols: (A) anterograde perfusion, adenosine via the portal vein; (B) anterograde perfusion, adenosine via the hepatic artery; (C) retrograde perfusion, adenosine via the hepatic vein; and (D) retrograde perfusion, adenosine via the hepatic artery. Due to the very pronounced concentration gradients generated by metabolic transformation, the infused adenosine attained maximal concentrations in different regions with each experimental protocol. The sinusoidal mean transit times (t̄ s) were not changed by adenosine in anterograde perfusion, but were increased in retrograde perfusion. It was concluded that the vasoconstrictive elements are localized essentially in the presinusoidal region. Glucose release stimulation presented two kinetic components. The first one was rapid in both onset and decay with a peak around 30 sec; the second one developed more slowly (several minutes). The factors of the first kinetic component are possibly generated in the presinusoidal region or in the first periportal cells. The initial decrease in oxygen consumption seemed to be localized in the region just after the intrasinusoidal confluence of the ramifications of the portal vein and hepatic artery. Indomethacin decreased glucose release stimulation by adenosine in both anterograde and retrograde perfusion only when DMSO was the vehicle. The participation of eicosanoids in the generation of the effects of adenosine seems to be less important than hitherto believed.