Peroxynitrite decreases arrhythmias induced by ischaemia reperfusion in anaesthetized dogs, without involving mitochondrial K ATP channels

A. Kiss, L. Juhász, I. Huliák, Å Végh

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Abstract

Background and purpose: Exogenous peroxynitrite from nanomolar to micromolar concentrations exerts cardioprotection. Here, we have assessed its effects on ischaemia- and reperfusion-induced ventricular arrhythmias in vivo and a possible role for mitochondrial K ATP channels in these effects, using the channel inhibitor 5-hydroxydecanoate (5-HD). Experimental approach: Chloralose-urethane-anaesthetized dogs were treated twice for 5 min with peroxynitrite (100 nM, by intracoronary infusions) in both the absence and presence of 5-HD (150 μg kg -1 min -1), and then subjected to 25 min occlusion of the left anterior descending coronary artery. The severity of ischaemia and of arrhythmias, as well as the levels of nitrotyrosine were assessed and compared with a group of control dogs, subjected only to a 25 min occlusion and reperfusion insult. Key results: Compared with controls, infusion of peroxynitrite markedly suppressed the number of ventricular premature beats (388±88 vs 133±44), the incidence of ventricular fibrillation both during occlusion (50% vs 10%) and reperfusion (100% vs 44%), and increased survival (0% vs 50%; all P<0.05). The severity of ischaemia (epicardial ST-segment changes, inhomogeneity of electrical activation) during occlusion and nitrotyrosine levels on reperfusion were significantly less in the peroxynitrite-treated dogs than in the controls. 5-HD did not modify the cardioprotective effects of peroxynitrite. Conclusion and implications: Exogenous peroxynitrite provided antiarrhythmic protection in vivo, which might have been on account of a reduction in endogenous peroxynitrite formation. This protection seemed not to be mediated through mitoK ATP channels.

Original languageEnglish
Pages (from-to)1015-1024
Number of pages10
JournalBritish journal of pharmacology
Volume155
Issue number7
DOIs
Publication statusPublished - Dec 1 2008

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Keywords

  • Arrhythmias
  • Free radicals
  • Mitochondrial K channels
  • Nitric oxide
  • Peroxynitrite

ASJC Scopus subject areas

  • Pharmacology

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