Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide.
Previous investigations have demonstrated that early preconditioning induced by nitroglycerin is mediated by calcitonin gene-related peptide (CGRP). In the present study, we addressed the question of whether delayed preconditioning induced by nitroglycerin in the rat is related to stimulation of the release and synthesis of CGRP. Sprague-Dawley rats were pretreated with nitroglycerin 24 h before the experiment. The left main coronary artery was occluded for 60 min, followed by 3 h reperfusion. Infarct size, serum creatine kinase activity, serum levels of NO and CGRP and the expression of alpha- and beta-CGRP isoform mRNA in lumbar dorsal root ganglia were measured. Pretreatment with nitroglycerin (60 or 120 microg/kg i.v.) reduced both the infarct size and the release of creatine kinase during reperfusion and caused a significant increase in the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA, concomitantly with an increase in concentrations of NO and CGRP. The increase in CGRP expression preceded the increase in CGRP release. The effects of nitroglycerin were abolished completely by pretreatment with methylene blue (30 mg/kg i.p.), an inhibitor of guanylate cyclase, or capsaicin (50 mg/kg s.c.), which selectively depletes transmitters in capsaicin-sensitive sensory nerves. The present results suggest that the delayed cardioprotection induced by nitroglycerin is mediated mainly by the alpha-CGRP isoform via the NO-cGMP pathway.
Zhou
Zhi-Hong
ZH
Department of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, Hunan 410078, People's Republic of China.
Peng
Jun
J
Ye
Feng
F
Li
Nian-Sheng
NS
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000097:blood; D002211:Capsaicin / Q000494:pharmacology; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009203:Myocardial Infarction / Q000378:metabolism* / Q000517:prevention & control; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D005996:Nitroglycerin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D012333:RNA, Messenger; D014665:Vasodilator Agents; D009569:Nitric Oxide; D003402:Creatine Kinase; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D008751:Methylene Blue