Nitric oxide regulation of myocardial O2 consumption and HEP metabolism

Jianyi Zhang, Guangrong Gong, Yun Ye, Tao Guo, Abdul Mansoor, Qingsong Hu, Koichi Ochiai, Jingbo Liu, Xiaohong Wang, Yarong Cheng, Nicole Iverson, Joseph Lee, Arthur H.L. From, Kamil Ugurbil, Robert J. Bache

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17 Scopus citations


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 (MV̇O2) 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 ω-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 MV̇O2, 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.

Original languageEnglish (US)
Pages (from-to)H310-H316
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1 57-1
StatePublished - Jan 2005


  • Heart
  • High-energy phosphate
  • Myocardial blood flow
  • Nuclear magnetic resonance spectroscopy
  • Phosphate


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