Calcitonin gene-related peptide-induced preconditioning protects against ischemia-reperfusion injury in isolated rat hearts.
Our previous work has suggested that the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) can abolish the protective effect of ischemic preconditioning in the isolated rat heart. Therefore we tested the hypothesis that CGRP- or capsaicin-induced preconditioning protects against ischemia-reperfusion injury in the isolated perfused rat heart. Thirty minutes of global ischemia and 30 min of reperfusion caused a significant cardiac contractile dysfunction, ventricular arrhythmia, and an increased release of creatine phosphate kinase. Pretreatment with CGRP or capsaicin, which evokes release of CGRP from cardiac sensory nerves, for 5 min produced a significant improvement of cardiac function, a reduction in the incidence of ventricular arrhythmia, and a decrease in the release of creatine phosphate kinase. However, the cardioprotection provided by CGRP- or capsaicin-induced preconditioning was abolished by CGRP-(8-37) and ruthenium red, respectively. These findings suggest that CGRP- or capsaicin-induced preconditioning protects against ischemic myocardial injury. The present results also suggest that CGRP may be an endogenous myocardial protective substance in the rat.
Department of Pharmacology, Hunan Medical University, Changsha, People's Republic of China.
Y J
YJ
Li
Z S
ZS
Xiao
C F
CF
Peng
H W
HW
Deng
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D003402:Creatine Kinase / Q000032:analysis; D004789:Enzyme Activation; D006339:Heart Rate / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology
D004396:Coloring Agents; D010446:Peptide Fragments; D012430:Ruthenium Red; C058636:calcitonin gene-related peptide (8-37); D003402:Creatine Kinase; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin