Nitric oxide synthase in porcine heart mitochondria: evidence for low physiological activity.
The capacity of isolated porcine heart mitochondria to produce nitric oxide (NO) via mitochondrial NO synthase (NOS) was evaluated. The mitochondrial NOS content and activity (0.2 nmol NO x mg mitochondrial protein(-1) x min(-1)) were approximately 10 times lower than previously reported for the rat liver. No evidence for mitochondrial NOS-generated NO was found in mitochondrial suspensions based on the lack of NO production and the lack of effect of either L-arginine or NOS inhibitors on the rate of respiration. The reason that even the low mitochondrial NOS activity did not result in net NO production and metabolic effects is because the mitochondrial metabolic breakdown of NO (1-4 nmol NO x mg mitochondrial protein(-1) x min(-1)) was greater than the maximum rate of NO production measured in homogenates. These data suggest that NO production at the mitochondria via NOS is not a significant source of NO in the intact heart and does not regulate cardiac oxidative phosphorylation.
French
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Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. frenchs@nih.gov
Giulivi
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Balaban
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D000818:Animals; D001120:Arginine / Q000494:pharmacology; D019069:Cell Respiration / Q000187:drug effects; D002956:Citrulline / Q000032:analysis / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D013552:Swine; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase