Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion injury: involvement of cytokine/chemokines and PMN

Journal of Leukocyte Biology

Francesco Rossi¹  Michele D’Amico¹  Settimio Rossi¹  Clara Di Filippo¹ 

[1] Department of Experimental Medicine, Section of Pharmacology “L. Donatelli,” Second University of Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology “L. Donatelli,” Second University of Naples, ItalyDepartment of Experimental Medicine, Section of Pharmacology “L. Donatelli,” Second University of Naples, Italy

关键词: heart infarct;    WIN55212-2;    IL-1β;    leukocytes;   

DOI  :  10.1189/jlb.0703303

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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-1β 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.

【 授权许可】

Unknown