Delayed preconditioning by cardiac ischemia involves endogenous calcitonin gene-related peptide via the nitric oxide pathway.
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.
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No. 110, Xiang-Ya Road Changsha, Hunan 410078, China.
Dan
D
Luo
Pan-Yue
PY
Deng
Feng
F
Ye
Wei-Jie
WJ
Peng
Han-Wu
HW
Deng
Yuan-Jian
YJ
Li
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D009569:Nitric Oxide; D003402:Creatine Kinase; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester