Abstract
During endotoxic shock, two endogenous cannabinoids, anandamide (ANA) and 2-arachidonoyl glycerol (2-AG), can be generated by activated macrophages and platelets and are thought to play a crucial role in the induction of shock-related hypotension. In vitro, the cell wall components of both Gram-positive and Gram-negative bacteria, can activate macrophages and release ANA. The aim of this study was to investigate whether cell wall components from Gram-positive bacteria could stimulate the release of ANA in an experimental animal model. Male Wistar rats were anesthetized and received an intravenous injection of lipoteichoic acid (LTA) and peptidoglycan (PepG) from Staphylococcus aureus. Mean arterial blood pressure (MAP) was monitored and blood samples were taken at 30 min and 360 min to measure ANA levels and other biochemical markers of multiple organ dysfunction syndrome (MODS) . The administration of LTA and PepG resulted in a significant increase in the serum concentration of ANA (360 min, n=4-6; P<0.05) and a biphasic fall in MAP from 103±1 mmHg (time 0) to 50±4 mmHg (360 min, n=5 ; P<0.05) . Furthermore, LTA+PepG was able to induce MODS as evidenced by a decrease in arterial oxygen tension (lung), an increase in serum levels of glutamate-pyruvate- and glutamate-oxaloacetatetransaminases (liver), and an increase in creatinine and blood urea nitrogen (kidney) . These results, together with those of previous studies, imply that ANA is an endogenous mediator of shock-induced hypotension, in response to both endotoxin and Gram-positive bacteria.
