Inhibition of cardiac tumor necrosis factor-alpha production by calcitonin gene-related peptide-mediated ischemic preconditioning in isolated rat hearts.

Abstract

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.

• Authors: J Peng, J Xiao, F Ye, H W Deng, Y J Li
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 407 Issue 3 Pg. 303-8 (Nov 03 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11068026 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channels
• Tumor Necrosis Factor-alpha
• Creatine Kinase
• Calcitonin Gene-Related Peptide

Topics

• Animals
• Calcitonin Gene-Related Peptide (pharmacology)
• Creatine Kinase (drug effects, metabolism)
• Hemodynamics (drug effects, physiology)
• Ischemic Preconditioning, Myocardial
• Male
• Myocardium (metabolism)
• Potassium Channels (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects, physiology)
• Tumor Necrosis Factor-alpha (drug effects, metabolism)