Antioxidant properties of pyruvate mediate its potentiation of β-adrenergic inotropism in stunned myocardium

M. Isabel Tejero-Taldo, James L. Caffrey, Jie Sun, Robert T. Mallet

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

This study tested the hypothesis that pyruvate's antioxidant actions, particularly its enhancement of the endogenous glutathione system, mediate its potentiation of β-adrenergic inotropism in stunned myocardium. Isolated working guinea pig hearts, metabolizing 10 mM glucose and stunned by 45 min of low flow ischemia, were treated with 5 mM pyruvate, 5 mM N-acetylcysteine (NAC) and/or 2 nM isoproterenol beginning 15 min after reperfusion. The antioxidant NAC alone did not increase cardiac power (mJ/min/g wet: 11 ± 1 in untreated and 15 ± 2 in NAC treated stunned hearts), but NAC potentiated the increase in power produced by 2 nM isoproterenol (isoproterenol alone: 50 ± 10: NAC plus isoproterenol: 133 ± 24). Addition of NAC doubled cyclic AMP content but lowered cytosolic phosphorylation potential by 32% in isoproterenol-stimulated hearts. Stunning decreased the glutathione antioxidant ratio (GSH/GSSG) by 68%. The antioxidant ratio was completely restored by pyruvate alone or in combination with isoproterenol, but only partially restored by isoproterenol alone. Combining isoproterenol and NAC increased the GSH/GSSG ratio by an additional 36%. The combined treatment of pyruvate and isoproterenol increased the NADPH/NADP+ ratio almost three-fold, and produced the greatest accumulation of glucose-6-phosphate of any treatment. Conclusions: like pyruvate, the antioxidant NAC potentiated β-adrenergic inotropism of stunned myocardium. Unlike pyruvate, NAC did not increase cellular energy reserves, thus effectively limiting its potentiation of β-adrenergic stimulation. Thus, pyruvate's potentiation of β-adrenergic stimulation in stunned myocardium is most likely the result of the combined effects of its antioxidant and energetic properties.

Original languageEnglish
Pages (from-to)1863-1872
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume31
Issue number10
DOIs
StatePublished - 1 Jan 1999

Keywords

  • Adenylate cyclase
  • Cardiac stunning
  • Cyclic AMP
  • Glutathione
  • Isoproterenol
  • N-acetylcysteine
  • Pyruvate

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