To determine whether beta-adrenergic receptors on circulating lymphocytes are impaired during endotoxemia and the precise role of catecholamines in this process, we allocated 16 dogs to three groups: I) control-saline vehicle (n = 5), II) endotoxin-Escherichia coli endotoxin 1.0 mg/kg iv bolus (n = 6), and III) endotoxin + propranolol-E. coli endotoxin 1.0 mg/kg after pretreatment with propranolol, 1.5 mg/kg iv bolus followed by a continuous infusion, 30 μg/kg per min, (n = 5). Five hours after endotoxin injection, lymphocytic beta-adrenergic receptor number and sodium fluoride (NaF)-stimulated cyclic AMP accumulation were reduced to 41 ± 6% and 25 ± 7% of baseline values, respectively, which were significantly different from those observed in the control group (both P < .01). Propranolol pretreatment prevented the endotoxin-induced reduction in lymphocytic beta-adrenergic receptor number (P < .02 compared with the endotoxin group), but not the decrease in NaF-stimulated cyclic AMP accumulation (P < .01 compared with the control group). Myocardial beta-adrenergic receptor number was reduced in the endotoxin group compared with that observed in the control group (P < .06). These changes were associated with a decreased chronotropic response to isoproterenol in the endotoxin group compared with the control group (P < .05). We conclude that decreased lymphocytic beta-adrenergic receptor number in endotoxin shock is caused by circulating catecholamines, whereas alterations distal to the receptors may be due to other mechanisms.
|Original language||English (US)|
|Number of pages||14|
|State||Published - Dec 1 1990|
- adrenergic blockade
- adrenergic desensitization
- cyclic AMP
- myocardial beta-adrenergic receptors