Myocardial postconditioning is lost in vascular nitrate tolerance

Veronika Fekete, Zsolt Murlasits, Eda Aypar, Péter Bencsik, Márta Sárközy, G. Szénási, P. Ferdinándy, T. Csont

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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
Volume62
Issue number3
DOIs
Publication statusPublished - Sep 2013

Fingerprint

Nitrates
Blood Vessels
Ischemic Postconditioning
Reperfusion
Phosphotransferases
Coronary Occlusion
Nitroglycerin
Nitric Oxide Synthase
Myocardial Ischemia
Wistar Rats
Myocardium
Ischemia
Phosphorylation

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Myocardial postconditioning is lost in vascular nitrate tolerance. / Fekete, Veronika; Murlasits, Zsolt; Aypar, Eda; Bencsik, Péter; Sárközy, Márta; Szénási, G.; Ferdinándy, P.; Csont, T.

In: Journal of Cardiovascular Pharmacology, Vol. 62, No. 3, 09.2013, p. 298-303.

Research output: Contribution to journalArticle

Fekete, Veronika ; Murlasits, Zsolt ; Aypar, Eda ; Bencsik, Péter ; Sárközy, Márta ; Szénási, G. ; Ferdinándy, P. ; Csont, T. / Myocardial postconditioning is lost in vascular nitrate tolerance. In: Journal of Cardiovascular Pharmacology. 2013 ; Vol. 62, No. 3. pp. 298-303.
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