Downregulation of hepatic beta-adrenergic receptors after trauma and hemorrhagic shock

Abstract

Although it is well known that sympathoadrenal activity increases under various adverse circulatory conditions, it is not known whether there are any alterations in hepatic plasma membrane beta-adrenergic receptors after trauma-hemorrhage and crystalloid resuscitation. To study this, rats underwent a 5-cm midline laparotomy (i.e., trauma induced) and 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 plasma membranes were isolated using discontinuous Percoll gradient centrifugation. The maximal binding capacity and dissociation constant (i.e., 1/affinity) of [125I]iodopindolol binding to beta-adrenergic receptors 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 despite crystalloid resuscitation after hemorrhage. However, there were no significant changes in the dissociation constant at any time point during this study. The downregulation of beta-adrenergic receptor binding capacity may be responsible for metabolic abnormalities observed after hemorrhagic shock.