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.
Li
Y J
YJ
Department of Pharmacology, Hunan Medical University, Changsha, People's Republic of China.
Xiao
Z S
ZS
Peng
C F
CF
Deng
H W
HW
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