Original Article

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 365, Issue 4, pp 253-259

Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide

  • Zhi-Hong ZhouAffiliated withDepartment of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, Hunan 410078, People's Republic of China
  • , Jun PengAffiliated withDepartment of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, Hunan 410078, People's Republic of China
  • , Feng YeAffiliated withDepartment of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, Hunan 410078, People's Republic of China
  • , Nian-Sheng LiAffiliated withDepartment of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, Hunan 410078, People's Republic of China
  • , Han-Wu DengAffiliated withDepartment of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, Hunan 410078, People's Republic of China
  • , Yuan-Jian LiAffiliated withDepartment of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, Hunan 410078, People's Republic of China

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract.

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 α- and β-CGRP isoform mRNA in lumbar dorsal root ganglia were measured. Pretreatment with nitroglycerin (60 or 120 µg/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 α-CGRP mRNA, but not β-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 α-CGRP isoform via the NO-cGMP pathway.

Nitroglycerin Delayed preconditioning CGRP (calcitonin gene-related peptide) Capsaicin Nitric oxide (NO) Methylene blue