Cannabinoid receptors (mainly type 2, CB2 receptors) are expressed abundantly on hemopoetic cell lines (T-lymphocytes) and in the cardiovascular system. Activation of CB2 receptors can lead directly to apoptosis. On the other hand, stimulation of CB2 receptors also stabilizes mitochondrial membranes and inhibits the release of inflammatory cytokines, thus actuation of CB2 receptors can exert anti-apoptotic effect as well. In the heart and vasculature, other cannabinoid-sensitive receptors (e.g. type 1 CB1 and vanilloid receptors) are present. Cannabinoids also represent antioxidant agents. Previously it was demonstrated that cannabinoids are cardioprotective in ischemic-reperfusion injury.

Our aim was to determine the influence of a non selective agonist – partial antagonist D9-tetrahydrocannabinol (THC) pretreatment on the cardiac function, oxidative-nitrative stress and poly (ADP-ribosyl)ation (PAR) in a rat model of sepsis. 300–350g male rats were intravenously administered with 5 mg/kg lipopolysaccharide (L) or its vehicle (C). A subset of endotoxemic animals received intraperitoneally 10 mg/kg tetrahydrocannabinol (T+L), immediately before endotoxin administration. The effect of THC was also tested on control animals. 24 hours later echocardiography was performed on the animals, malonyl-dialdehyde assay (MDA) was performed on the sera samples, and nitrotyrosine and PAR immunostaining was carried out on lymphocyte smears (staining intensity was scored from 1 to 10 by blinded experimenter). End-systolic and end-diastolic volumes (ESV, EDV) and the diameter of left ventricle (LVIDd) were decreased in L group (ESV: 0.061 ± 0.018, 0.03 ±0.01 ml, p <0.01 vs C; EDV: 0.33±0.05, 0.2±0.02 ml p <0.05 vs. C; 6.15 ± 0.9, 5.09 ± 0.5mm p <0.05 vs. C, mean±SEM). THC improved ESV, EDV and LVIDd (0.056 ± 0.01 ml p <0.05 vs. L, 0.34±0.08 ml; 5.99 ± 0.6mm). MDA levels were elevated in L group (67.1 ± 25.2 vs. 207.6 ± 81.7 mM, p <0.01 vs. C) THC tended to decrease oxidative stress (T+L: 111.7 ± 73.3 mM). Nitrotirosine and PAR-results followed the patterns of MDA measurements. In control rats, THC treatment had no effect on the studied parameters. THC treatment improved cardiac function, reduced oxidative-nitrative stress and consequent PAR-ation in endotoxemic rats. Therefore it can be assumed that THC pretreatment influences cardiovascular status partly through the reduction of oxidative stress.