Does Infusion of Bacillus anthracis Toxins Produce Sympathoinhibition?

Abstract

Bacillus anthracis infection is a pathophysiological condition that produces shock‐like cardiovascular alterations. Bacillus anthracis produces two endotoxins, lethal toxin (LeTx; lethal factor + protective antigen) and edema toxin. Neurological complications are a critical component of the pathology produced by Bacillus anthracis toxins, however, little is known about the effect of these toxins on sympathetic nerve regulation. We tested the hypothesis that infusions of Bacillus anthracis toxins alter sympathetic nerve discharge (SND). Splenic, renal, and adrenal SND were recorded in urethane‐chloralose anesthetized rats. Rats with intact or denervated arterial baroreceptors (SAD) received intravenous lethal factor (100 μg/kg) + protective antigen (200 μg/kg) (LeTx) or vehicle, infused at 0.5 ml/hr. Mean arterial pressure (MAP), heart rate (HR), and SND were recorded continuously (up to 6 hrs) before and during intravenous toxin or vehicle infusions. Results indicate that LeTx produced marked reductions in MAP and HR that occurred several hours after initiation of infusion. The reduction in MAP was accompanied by inhibition of SND in both baroreceptor‐intact and SAD rats, indicating LeTx‐induced dysregulation of SND. These preliminary data provide evidence suggesting that Bacillus anthracis toxins can alter regulation of sympathetic nerve outflow. Funding provided by NIH HL092392.