Inhibition of cardiac tumor necrosis factor-alpha production by calcitonin gene-related peptide-mediated ischemic preconditioning in isolated rat hearts.
Previous investigations have demonstrated that calcitonin gene-related peptide (CGRP) 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-alpha (TNF-alpha) in myocardial tissues. However, ischemic preconditioning (three 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-alpha 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 potassium (K(ATP)) 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-alpha production, but not to activation of the K(ATP) channel.
Peng
J
J
Department of Pharmacology, Hunan Medical University, Hunan 410078, Changsha, People's Republic of China.
Xiao
J
J
Ye
F
F
Deng
H W
HW
Li
Y J
YJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D003402:Creatine Kinase / Q000187:drug effects* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D015221:Potassium Channels; D014409:Tumor Necrosis Factor-alpha; D003402:Creatine Kinase; D015740:Calcitonin Gene-Related Peptide