AJP - Gastrointestinal and Liver Physiology, Vol 268, Issue 5 749-G753, Copyright © 1995 by American Physiological Society
Downregulation of hepatic beta-adrenergic receptors after trauma and hemorrhagic shock
S. M. Tait, P. Wang, Z. F. Ba and I. H. Chaudry
Department of Surgery, Michigan State University, East Lansing 48824, USA.
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.
