Nitrite oxidation of myoglobin in perfused myocardium: implications for energy coupling in respiration.
Nitrite oxidation of oxymyoglobin in perfused rat myocardium under nonlimiting oxygen produces a detectable 1H nuclear magnetic resonance metmyoglobin (metMb) signal at -3.9 ppm. When the myocardium is perfused with < 10 mM nitrite, the 1H nuclear magnetic resonance MbO2 gamma CH3 Val E11 signal does not change intensity and the metMb reporter signal at -3.9 ppm is undetectable. However the rate pressure product decreases by 26% from the control level. Phosphocreatine, myocardial oxygen consumption, Pi, ATP, and pH remain constant. With > 10 mM infused nitrite, myoglobin (Mb) oxidation becomes apparent. As the MbO2 gamma CH3 Val E11 signal intensity decreases, the metMb signal intensity at -3.9 ppm increases. At the same time the 31P high-energy phosphate signals, rate pressure product, and lactate formation exhibit significant alterations. Myocardial oxygen consumption, however, remains constant. The data indicate that Mb oxidation does not limit myocardial respiration but does reduce energy production. Pulse-recovery experiments further demonstrate that a transient perfusion with 2 mM infused nitrite depresses the contractile function, which does not recover during reperfusion with oxygenated, nitrite-free buffer. The findings support the view that either Mb mediates energy coupling or nitrite directly uncouples energy production in myocardium. They also reveal a glimpse of the intracellular reductase activity that maintains the Mb in the Fe (II) state.
Chung
Y
Y
Biological Chemistry Department, University of California, Davis 95616-8635, USA.
Xu
D
D
Jue
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004734:Energy Metabolism; D006339:Heart Rate / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects
D009211:Myoglobin; D009573:Nitrites; D010710:Phosphates; D010725:Phosphocreatine