Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion injury: involvement of cytokine/chemokines and PMN.
In this study, we have assessed the activation of the cannabinoid CB2 receptor (CB2-R) in a model of mouse myocardial ischemia/reperfusion (I/R). The results show that treatment of animals with WIN55212-2, a CB1/CB2-R agonist, given 30 min before induction of I/R, significantly reduced the extent of infarct size (IS) in the area at risk, as measured 2.5 h later, with almost a 51% inhibition observed at the dose tested of 3.5 mg/kg intraperitoneally (i.p.). The protective effect of WIN55212-2 was almost abolished by the selective CB2-R antagonist AM630 (1 mg/kg i.p.) and not affected by the selective CB1-R antagonist AM251 (3 mg/kg i.p.). The CB2-R antagonist administered alone produced a slight but significant (P<0.05) increase in IS compared with vehicle alone. The protection afforded by WIN55212-2 was paralleled by lower values of myeloperoxidase activity and interleukin-1beta and of the CXC chemokine ligand 8 into the injured tissue. In conclusion, we demonstrate for the first time that exogenous and endogenous CB2-R activation reduces the leukocyte-dependent myocardial damage associated with an I/R procedure.
Di Filippo
Clara
C
Department of Experimental Medicine, Section of Pharmacology L Donatelli, Second University of Naples, Italy.
Rossi
Francesco
F
Rossi
Settimio
S
D'Amico
Michele
M
D000818:Animals; D018925:Chemokines / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000032:analysis; D020011:Protective Agents; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018925:Chemokines; D016207:Cytokines; D007375:Interleukin-1; D020011:Protective Agents; D043885:Receptor, Cannabinoid, CB2; D009195:Peroxidase