Effect of lethal doses of bacterial endotoxin (E. coli) on sympathetic neurohormones in the rabbit

¹ Pharmacology Section, Department of Chemistry, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D. C.

Lethal doses of E. coli endotoxin, administered intravenously, produced an immediate, precipitous fall in blood pressure, which returned to near normal levels over the next hour. Approximately 1 hour after endotoxin administration the blood pressure began to fall gradually and continued to fall until the death of the animal. During the period of immediate blood pressure fall there was no significant increase in the circulating catecholamines and no decrease in the adrenal content of these hormones. This suggests that the sympathetic nervous system may be depressed during the initial phases of endotoxin poisoning so that the sympathetic discharge which is seen during hypotension, produced by other means, is inoperative. When the pressure returned to near normal levels, the circulating catecholamine concentrations were elevated and the adrenal gland content of these materials was decreased. When the pressure dropped to levels below 60 mm Hg, 4–6 hours after endotoxin administration, the circulating catecholamine level was still statistically elevated and the adrenal content of catecholamines was further depressed. These experiments demonstrate that the blood pressure levels, during endotoxin administration, do not parallel expected peripheral catecholamine concentrations. During the late stages of endotoxin poisoning there is evidence that the animal becomes refractive to increased endogenous epinephrine and norepinephrine.