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This Article Full Text Full Text (PDF) All Versions of this Article: 288/1/H310    most recent 00518.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Zhang, J. Articles by Bache, R. J. Search for Related Content PubMed PubMed Citation Articles by Zhang, J. Articles by Bache, R. J.

Nitric oxide regulation of myocardial O₂ consumption and HEP metabolism

Departments of Medicine, Biochemistry, and Radiology and Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota

Submitted 3 June 2004 ; accepted in final form 9 September 2004

NO and O₂ compete at cytochrome-c oxidase, thus potentially allowing NO to modulate mitochondrial respiration. We previously observed a decrease of myocardial phosphocreatine (PCr)/ATP during very high cardiac work states, corresponding to an increase in cytosolic free ADP. This study tested the hypothesis that NO inhibition of respiration contributes to this increase of ADP. Infusion of dobutamine + dopamine (DbDp, each 20 µg·kg^–1·min^–1 iv) to more than double myocardial oxygen consumption (MO₂) in open-chest dogs caused a decrease of myocardial PCr/ATP measured with ³¹P NMR from 2.04 ± 0.09 to 1.85 ± 0.08 (P < 0.05). Inhibition of NO synthesis with N-nitro-L-arginine (L-NNA), while catecholamine infusion continued, caused PCr/ATP to increase to the control value. In a second group of animals, L-NNA administered before catecholamine stimulation (reverse intervention of the first group) increased PCr/ATP during basal conditions. In these animals L-NNA did not prevent a decrease of PCr/ATP at the high cardiac work state but, relative to MO₂, PCr/ATP was significantly higher after L-NNA. In a third group of animals, pharmacological coronary vasodilation with carbochromen was used to prevent changes in coronary flow that might alter endothelial NO production. In these animals L-NNA again restored depressed myocardial PCr/ATP during catecholamine infusion. The finding that inhibition of NO production increased PCr/ATP suggests that during very high work states NO inhibition of mitochondrial respiration requires ADP to increase to drive oxidative phosphorylation.

nuclear magnetic resonance spectroscopy; high-energy phosphate; heart; phosphate; myocardial blood flow

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