DOWN-REGULATION OF HEPATIC BETA-ADRENERGIC RECEPTORS AFTER TRAUMA ANDHEMORRHAGIC-SHOCK

Although it is well known that sympathoadrenal activity increases unde r various adverse circulatory conditions, it is not known whether ther e are any alterations in hepatic plasma membrane beta-adrenergic recep tors after trauma-hemorrhage and crystalloid resuscitation. To study t his, rats underwent a 5-cm midline laparotomy (i.e., trauma induced) a nd were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximal bleedout (MB) volume was returned in the form of Ringer lactate. The animals were then resuscitated with four times the volume of MB in the form of Ringer lactate over 60 min. Hepatic p lasma membranes were isolated using discontinuous Percoll gradient cen trifugation. The maximal binding capacity and dissociation constant (i .e., 1/affinity) of [I-125]iodopindolol binding to beta-adrenergic rec eptors were determined using a membrane filtration assay and Scatchard analysis. The results indicate that there was a significant decrease in the maximal binding capacity at the time of MB, which persisted des pite crystalloid resuscitation after hemorrhage. However, there were n o significant changes in the dissociation constant at any time point d uring this study. The downregulation of beta-adrenergic receptor bindi ng capacity may be responsible for metabolic abnormalities observed af ter hemorrhagic shock.