Anandamide enhances expression of heat shock protein 72 to protect against ischemia-reperfusion injury in rat heart.

Anandamide (AEA), one of endocannabinoids, has been reported to exhibit a cardioprotective ability to limit the damage produced by ischemia-reperfusion injury. AEA reportedly enhanced heat shock protein 72 (HSP72) and HSP25 expression in lungs to protect against lung inflammation. This study tested the hypothesis that intravenously injected AEA would induce HSP72 in the heart and thus render cardioprotection against ischemia-reperfusion injury in rats. Cardiac expression of HSPs was quantitatively evaluated in rats by Western blot analysis. That intravenously injected AEA 1 mg/kg in vivo induced expression of HSP72, which peaked at 24 h after administration. The enhancement of HSP72 by AEA was blocked by cannabinoid 2 (CB(2)) receptor antagonist AM630, but not cannabinoid 1 (CB(1)) receptor antagonist AM251. Therefore, the rats were induced with a 30-min coronary occlusion followed by a 120-min reperfusion in vivo at 24 h after administration of drugs or vehicle, and then the infarct size was measured. AEA reduced myocardial infarct size compared to control group. Pretreatment with AM630 but not AM251 abolished the infarct size-limiting effect of AEA. Further study demonstrated pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, Akt inhibitor MK-2206 and AM630 attenuated phosphorylation of Akt and AEA-induced HSP72 expression. The results suggest that AEA is cardioprotective against ischemia-reperfusion insult through its induction of HSP72, which might be mediated by the PI3K/Akt signaling pathway. These effects were mediated by CB(2) but not CB(1) receptors.