Nitric oxide regulation of myocardial O2 consumption and HEP metabolism.
NO and O(2) 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 microg.kg(-1).min(-1) iv) to more than double myocardial oxygen consumption (MVo(2)) in open-chest dogs caused a decrease of myocardial PCr/ATP measured with (31)P NMR from 2.04 +/- 0.09 to 1.85 +/- 0.08 (P < 0.05). Inhibition of NO synthesis with N(omega)-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 MVo(2), 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.
Zhang
Jianyi
J
Department of Medicine, Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN 55455, USA. zhang047@umn.edu
Gong
Guangrong
G
Ye
Yun
Y
Guo
Tao
T
Mansoor
Abdul
A
Hu
Qingsong
Q
Ochiai
Koichi
K
Liu
Jingbo
J
Wang
Xiaohong
X
Cheng
Yarong
Y
Iverson
Nicole
N
Lee
Joseph
J
From
Arthur H L
AH
Ugurbil
Kamil
K
Bache
Robert J
RJ
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology*; D010725:Phosphocreatine / Q000378:metabolism*
D010725:Phosphocreatine; D009569:Nitric Oxide; D000244:Adenosine Diphosphate