Delayed cardioprotection afforded by nitroglycerin is mediated by alpha-CGRP via activation of inducible nitric oxide synthase.
Previous investigations have demonstrated that delayed preconditioning induced by nitroglycerin is mediated by endogenous calcitonin gene-related peptide (CGRP). In the present study, we examined whether CGRP-mediated delayed preconditioning induced by nitroglycerin is involved in activation of inducible nitric oxide synthase (iNOS). Male Wistar rats were pretreated with nitroglycerin 24 h before the experiment, and then the left main coronary artery of rat heart was subjected to 60-min occlusion followed by 3 h reperfusion. Infarct size, the plasma level of cGMP and CGRP, and expression of CGRP isoforms (alpha-CGRP and beta-CGRP) mRNA in lumbar dorsal root ganglia were measured. Pretreatment with nitroglycerin (120 microg/kg, i.v.) markedly reduced infarct size. Nitroglycerin caused a significant increase in the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA, concomitant with an increase in plasma concentrations of cGMP and CGRP. These effects of nitroglycerin were completely abolished by pretreatment with aminoguanidine (300 mg/kg, i.p.), a selective inhibitor of iNOS activity, or dexamethasone (5 mg/kg, i.p.), the iNOS expression inhibitor. The present results suggest that delayed cardioprotection afforded by nitroglycerin is mediated by the alpha-CGRP isoform via generation of NO derived from iNOS.
Du
Yan-Hua
YH
Department of Pharmacology, School of Pharmaceutic Sciences, Central South University, Xiang-Ya Road 88#, Changsha, Hunan 410078, China.
Peng
Jun
J
Huang
Zhi-Zhuang
ZZ
Jiang
De-Jian
DJ
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000517:prevention & control; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide