M I Tejero-Taldo1, J L Caffrey, J Sun, R T Mallet. 1. Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, Texas 76107-2699, USA.
Abstract
UNLABELLED: This study tested the hypothesis that pyruvate's antioxidant actions, particularly its enhancement of the endogenous glutathione system, mediate its potentiation of beta-adrenergic inotropism in stunned myocardium. Isolated working guinea pig hearts, metabolizing 10 m M glucose and stunned by 45 min of low flow ischemia, were treated with 5 m M pyruvate, 5 m M N-acetylcysteine (NAC) and/or 2 n M 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 n M 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 beta-adrenergic inotropism of stunned myocardium. Unlike pyruvate, NAC did not increase cellular energy reserves, thus effectively limiting its potentiation of beta-adrenergic stimulation. Thus, pyruvate's potentiation of beta-adrenergic stimulation in stunned myocardium is most likely the result of the combined effects of its antioxidant and energetic properties. Copyright 1999 Academic Press.
UNLABELLED: This study tested the hypothesis that pyruvate's antioxidant actions, particularly its enhancement of the endogenous glutathione system, mediate its potentiation of beta-adrenergic inotropism in stunned myocardium. Isolated working guinea pig hearts, metabolizing 10 m M glucose and stunned by 45 min of low flow ischemia, were treated with 5 m M pyruvate, 5 m M N-acetylcysteine (NAC) and/or 2 n M 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 n M 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 beta-adrenergic inotropism of stunned myocardium. Unlike pyruvate, NAC did not increase cellular energy reserves, thus effectively limiting its potentiation of beta-adrenergic stimulation. Thus, pyruvate's potentiation of beta-adrenergic stimulation in stunned myocardium is most likely the result of the combined effects of its antioxidant and energetic properties. Copyright 1999 Academic Press.
Authors: Benjamin Hack; Paul K Witting; Benjamin S Rayner; Roland Stocker; John P Headrick Journal: Mol Cell Biochem Date: 2006-05-23 Impact factor: 3.396
Authors: David A Brown; Miguel A Aon; Chad R Frasier; Ruben C Sloan; Andrew H Maloney; Ethan J Anderson; Brian O'Rourke Journal: J Mol Cell Cardiol Date: 2009-12-03 Impact factor: 5.000