TY - JOUR
T1 - Delayed preconditioning by cardiac ischemia involves endogenous calcitonin gene-related peptide via the nitric oxide pathway
AU - Luo, Dan
AU - Deng, Pan Yue
AU - Ye, Feng
AU - Peng, Wei Jie
AU - Deng, Han Wu
AU - Li, Yuan Jian
PY - 2004/10/11
Y1 - 2004/10/11
N2 - Previous investigations have shown separately that calcitonin gene-related peptide (CGRP) or nitric oxide (NO) is involved in mediation of ischemic preconditioning. In the present study, we tested interactions of CGRP with NO in mediation of delayed preconditioning. In Sprague-Dawley rats, ischemia-reperfusion injury was induced by 45-min occlusion followed by 3-h reperfusion of coronary artery, and preconditioning was induced by four cycles of 3-min ischemia and 5-min reperfusion. Infarct size, plasma creatine kinase activity, the plasma level of NO and CGRP, and the expression of CGRP mRNA in dorsal root ganglion were measured. Pretreatment with preconditioning significantly reduced infarct size and the release of creatine kinase during reperfusion, and caused a significant increase in the expression of CGRP mRNA, concomitantly with an elevation in the plasma level of CGRP and NO. The effects of preconditioning were completely abolished by administration of l-nitroarginine methyl ester (l-NAME, 10 mg/kg, i.p.), an inhibitor of NO synthase. Pretreatment with capsaicin (50 mg/kg, s.c.), which depletes transmitters in capsaicin-sensitive sensory nerves, also blocked the cardioprotection of preconditioning and reduced the synthesis and release of CGRP, but did not affect the concentration of NO. The present results suggest the delayed protection afforded by ischemic preconditioning is also mediated by endogenous CGRP via the NO pathway in rat heart.
AB - Previous investigations have shown separately that calcitonin gene-related peptide (CGRP) or nitric oxide (NO) is involved in mediation of ischemic preconditioning. In the present study, we tested interactions of CGRP with NO in mediation of delayed preconditioning. In Sprague-Dawley rats, ischemia-reperfusion injury was induced by 45-min occlusion followed by 3-h reperfusion of coronary artery, and preconditioning was induced by four cycles of 3-min ischemia and 5-min reperfusion. Infarct size, plasma creatine kinase activity, the plasma level of NO and CGRP, and the expression of CGRP mRNA in dorsal root ganglion were measured. Pretreatment with preconditioning significantly reduced infarct size and the release of creatine kinase during reperfusion, and caused a significant increase in the expression of CGRP mRNA, concomitantly with an elevation in the plasma level of CGRP and NO. The effects of preconditioning were completely abolished by administration of l-nitroarginine methyl ester (l-NAME, 10 mg/kg, i.p.), an inhibitor of NO synthase. Pretreatment with capsaicin (50 mg/kg, s.c.), which depletes transmitters in capsaicin-sensitive sensory nerves, also blocked the cardioprotection of preconditioning and reduced the synthesis and release of CGRP, but did not affect the concentration of NO. The present results suggest the delayed protection afforded by ischemic preconditioning is also mediated by endogenous CGRP via the NO pathway in rat heart.
KW - Calcitonin gene-related peptide (CGRP)
KW - Capsaicin
KW - Ischemia-reperfusion
KW - Ischemic preconditioning
KW - Nitric oxide (NO)
UR - http://www.scopus.com/inward/record.url?scp=4744350974&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2004.08.051
DO - 10.1016/j.ejphar.2004.08.051
M3 - Article
C2 - 15464099
AN - SCOPUS:4744350974
SN - 0014-2999
VL - 502
SP - 135
EP - 141
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-2
ER -