NITRITE OXIDATION OF MYOGLOBIN IN PERFUSED MYOCARDIUM - IMPLICATIONS FOR ENERGY COUPLING IN RESPIRATION

Nitrite oxidation of oxymyoglobin in perfused rat myocardium under non limiting oxygen produces a detectable H-1 nuclear magnetic resonance m etmyoglobin (metMb) signal at -3.9 ppm. When the myocardium is perfuse d with <10 mM nitrite, the H-1 nuclear magnetic resonance MbO(2) gamma CH3 Val E11 signal does not change intensity and the metMb reporter s ignal at -3.9 ppm is undetectable. However the rate pressure product d ecreases by 26% from the control level. Phosphocreatine, myocardial ox ygen consumption, P-i, ATP, and pH remain constant. With >10 mM infuse d nitrite, myoglobin (Mb) oxidation becomes apparent. As the MbO(2) ga mma CH3 Val E11 signal intensity decreases, the metMb signal intensity at -3.9 ppm increases. At the same time the P-31 high-energy phosphat e signals, rate pressure product, and lactate formation exhibit signif icant alterations. Myocardial oxygen consumption, however, remains con stant. The data indicate that Mb oxidation does not limit myocardial r espiration but does reduce energy production. Pulse-recovery experimen ts further demonstrate that a transient perfusion with 2 mM infused ni trite depresses the contractile function, which does not recover durin g reperfusion with oxygenated, nitrite-free buffer. The findings suppo rt the view that either Mb mediates energy coupling or nitrite directl y uncouples energy production in myocardium. They also reveal a glimps e of the intracellular reductase activity that maintains the Mb in the Fe (II) state.