Adenosine formation and myocardial energy status during graded hypoxia.
Previous studies using hypoperfusion and 2-deoxyglucose infusion have revealed a biphasic relationship between myocardial energy status and adenosine release (RADO). As energy charge ([ATP] + 1/2[ADP])/([ATP] + [ADP] + [AMP]) or phosphorylation potential ([ATP]/[ADP][Pi]) is lowered there is an initial increase in RADO, but RADO declines from peak levels during severe energy depletion. This study examined the hypothesis that the same pattern of RADO exists during graded hypoxia. Isolated guinea-pig hearts were perfused at constant flow and exposed to mild (30% O2) and severe (0% O2) hypoxia in the presence of norepinephrine (NE, 6 x 10(-8) M). Phosphorylation potential and energy charge were determined using 31P-NMR spectroscopy and adenosine release into coronary venous effluent was measured. Graded hypoxia lowered energy charge and phosphorylation potential, and raised RADO. Although severe hypoxia plus NE lowered energy charge and phosphorylation potential to levels equivalent to those associated with decreased RADO during hypoperfusion or 2-deoxyglucose treatment, RADO during severe hypoxia was greater than during mild hypoxia. HCl was infused during severe hypoxia in order to reproduce the low intracellular pH seen during hypoperfusion, but HCl increased RADO rather than decreasing it. We conclude that during hypoxia, RADO does not have a biphasic relationship to phosphorylation potential or energy charge, suggesting that the regulation of adenosine formation cannot be explained solely in terms of these variables. Furthermore, intracellular acidosis is not responsible for inhibiting RADO at low phosphorylation potential and energy charge during hypoperfusion because it has no effect on RADO during severe hypoxia.
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Department of Physiology, Michigan State University, East Lansing 48824.
Gorman
M W
MW
Romig
G D
GD
Sparks
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HV
D000241:Adenosine / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D006168:Guinea Pigs; D006439:Hemodynamics; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine; D010101:Oxygen Consumption; D010766:Phosphorylation
D000249:Adenosine Monophosphate; D000241:Adenosine; D009638:Norepinephrine