Effects of canine endotoxin shock on lymphocytic beta-adrenergic receptors.
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 micrograms/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 by 41 +/- 6% and 25 +/- 7% of baseline values, respectively, which were significantly different from those observed in the control group (both P less than .01). Propranolol pretreatment prevented the endotoxin-induced reduction in lymphocytic beta-adrenergic receptor number (P less than .02 compared with the endotoxin group), but not the decrease in NaF-stimulated cyclic AMP accumulation (P less than .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 less than .06). These changes were associated with a decreased chronotropic response to isoproterenol in the endotoxin group compared with the control group (P less than .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.
Silverman
H J
HJ
Department of Medicine, School of Medicine, University of Maryland, Baltimore 21201.
Lee
N H
NH
el-Fakahany
E E
EE
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004731:Endotoxins / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism*; D014115:Toxemia / Q000378:metabolism
D004731:Endotoxins; D011943:Receptors, Adrenergic, beta; C044101:endotoxin, Escherichia coli; D011433:Propranolol; D000242:Cyclic AMP