Mechanism and significance of endotoxin-induced sensitization to acetylcholine in rabbits

¹ Naval Biological Laboratory, School of Public Health, University of California, Berkeley, California

An earlier report described a sensitization of pulmonary vasoconstrictor mechanisms (PVM) to circulating acetylcholine (ACh) in rabbits injected with Pseudomonas pseudomallei endotoxin. Preliminary studies showed that the sensitization was induced also by endotoxin from other gram-negative bacilli. The mechanism of sensitization and its significance are analyzed in this study. The effect was specific for ACh, unaltered by elimination of reflex mechanisms, and could be obtained in heart-lung preparations. Antihistaminic and adrenergic blocking agents did not abolish the phenomenon. Sensitization to ACh was not attributed to ACh-esterase inhibition. Atropine reduced or eliminated the enhanced responses to ACh after endotoxin but had no effect on the progressive fall in systemic arterial pressure to shock levels or on the lethality of endotoxin. It was concluded that endotoxin-induced sensitization of PVM to circulating ACh did not play a major role in endotoxin shock.

Key Words: endotoxin shock • Pseudomonas pseudomallei • melioidosis • pulmonary blood circulation • vascular smooth muscle • autonomic system • acetylcholinesterase • gram-negative bacteria • hyperreactivity to acetylcholine

Submitted on October 30, 1963