Myocardial postconditioning is lost in vascular nitrate tolerance

Veronika Fekete, Zsolt Murlasits, Eda Aypar, Péter Bencsik, Márta Sárközy, Gábor Szénási, Péter Ferdinandy, Tamás Csont

Research output: Contribution to journalArticle

11 Citations (Scopus)


ABSTRACT:: Organic nitrates play an important role in the therapy of ischemic heart disease; however, their clinical application is limited by the development of vascular nitrate tolerance. We have previously shown attenuation of the cardioprotective effect of preconditioning in vascular nitrate tolerance. Here, we studied whether the development of vascular nitrate tolerance affects the infarct size, limiting effect of ischemic postconditioning (IPost) in the myocardium, and whether the activation of survival kinases plays a role in the molecular mechanism of postconditioning in the presence or absence of vascular nitrate tolerance. Male Wistar rats were treated with nitroglycerin/vehicle for 3 days to induce vascular nitrate tolerance. On the fourth day, isolated hearts were subjected to 30-minute coronary occlusion followed by 120-minute reperfusion with or without IPost. In nontolerant hearts, postconditioning significantly decreased infarct size as compared with ischemia/reperfusion; however, postconditioning failed to decrease infarct size in hearts of nitrate tolerant rats. Phosphorylation of ERK 1/2, Akt, or endothelial nitric oxide synthetase showed no significant differences between the groups at the 10th minute of reperfusion. Vascular nitrate tolerance interferes with the infarct size limiting effect of IPost. Activation of survival kinases is not crucial in the molecular mechanism of postconditioning, which remains unaffected in nitrate tolerance.

Original languageEnglish
Pages (from-to)298-303
Number of pages6
JournalJournal of cardiovascular pharmacology
Issue number3
Publication statusPublished - Sep 1 2013


  • Infarct size
  • Nitrate tolerance
  • Nitroglycerin
  • Postconditioning
  • RISK pathway
  • Survival kinase

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Myocardial postconditioning is lost in vascular nitrate tolerance'. Together they form a unique fingerprint.

  • Cite this