Inhibition of cardiac tumor necrosis factor-a production by calcitonin gene-related peptide-mediated ischemic preconditioning in isolated rat hearts
European Journal of Pharmacology 407 2000. 303-308，-0001，（）：
Previous investigations have demonstrated that calcitonin gene-related peptideCGRP.plays an important role in the mediation of ischemic preconditioning in rats. In the present study, we examined signal transduction pathways of CGRP-mediated ischemic preconditioning. Thirty minutes of global ischemia and 40 min of reperfusion caused a dramatic decrease in myocardial function, and a significant increase in the release of cardiac creatine kinase in the coronary effluent and in the content of tumor necrosis factor-a TNF-a.in myocardial tissues. However, ischemic preconditioninghree cycles of 5-min ischemia and 5-min reperfusion.or pretreatment with CGRP for 5 min dramatically improved the recovery of cardiac function, and reduced the release of cardiac creatine kinase and the TNF-a content. The effect of ischemic preconditioning was abolished by CGRP-8-37., the selective CGRP receptor antagonist, and by capsaicin, which depletes sensory nerve neurotransmitter content, but was unaltered by treatment with glibenclamide, a blocker of the ATP-sensitive potassiumKATP.channel. The protective effects of exogenous CGRP-induced preconditioning were also not blocked by glibenclamide. These results suggest that the cardioprotective effects afforded by CGRP-mediated ischemic preconditioning are related to inhibition of cardiac TNF-a production, but not to activation of the KATP channel.