Peroxynitrite impairs cardiac contractile function by decreasing cardiac efficiency.
Peroxynitrite (ONOO-) inhibits energy metabolism in isolated cells and mitochondria and may be involved in the depression of cardiac mechanical function during pathophysiological states. We determined the actions of ONOO- on cardiac function and energy metabolism in isolated working rat hearts and compared them with the NO donor S-nitroso-DL-acetylpenicillamine (SNAP). After a 15-min baseline aerobic perfusion, ONOO- (4 or 40 microM), SNAP (40 microM), or their vehicles were infused over a 60-min period. ONOO- or SNAP (40 microM each) caused a rapid and sustained rise in coronary flow. Infusion of 40 microM (but not 4 microM) ONOO- caused a marked depression in cardiac work with a delayed onset but no change in O2 consumption, resulting in a marked loss of cardiac efficiency. Cardiac work, O2 consumption, and cardiac efficiency remained constant in vehicle- and SNAP-treated hearts. ONOO- (40 microM) enhanced glycolysis and glucose oxidation but did not change pyruvate oxidation compared with its vehicle control, whereas SNAP was without effect. ONOO(-)-mediated depression in cardiac efficiency may be due to reduced coupling between ATP production and mechanical work.
Schulz
R
R
Department of Pediatrics, University of Alberta, Edmonton, Canada. richard.schulz@ualberta.ca
Dodge
K L
KL
Lopaschuk
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GD
Clanachan
A S
AS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine
D009566:Nitrates; D011773:Pyruvates; D010725:Phosphocreatine; D009243:NAD; C039642:peroxynitric acid; D026423:S-Nitroso-N-Acetylpenicillamine; D000255:Adenosine Triphosphate; D010396:Penicillamine; D005947:Glucose