DIFFERENTIAL ALTERATIONS IN CYCLIC-NUCLEOTIDE LEVELS IN KUPFFER CELLSAND HEPATOCYTES FOLLOWING TRAUMA-HEMORRHAGE AND RESUSCITATION

Although cyclic nucleotides play an important role in regulating the c ontrol of metabolism, it is not known whether there are any differenti al alterations in cyclic nucleotides in Kupffer cells and hepatocytes after trauma-hemorrhage and resuscitation. To study this, rats underwe nt laparotomy (i.e., trauma-induced) and were rapidly bled to and main tained at a mean arterial pressure of 40 mmHg until 40% of maximum ble edout volume was returned in the form of Ringer's lactate. The animals were then resuscitated with Ringer's lactate, equivalent to four time s the volume of shed blood. At the time of maximum bleedout or at 1.5 h postresuscitation, a portion of the liver was removed, and the level s of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monoph osphate (cGMP) were determined by radioimmunoassay. Moreover, Kupffer cells and hepatocytes were isolated in additional groups of animals an d cAMP and cGMP levels were measured. The results indicate that hepati c cAMP decreased, whereas hepatic cGMP increased significantly at the time of maximum bleedout. Although resuscitation normalized hepatic cy clic nucleotide levels, the levels of cAMP and cGMP in Kupffer cells i ncreased significantly at 1.5 h after resuscitation. In contrast, cAMP and cGMP levels in hepatocytes were not significantly different from shams under such conditions. Thus, differential alterations in cyclic nucleotide levels in different liver cell populations occur following traumahemorrhage and resuscitation.