Dissociation between adenosine release, MVO2, and energy status in working guinea pig hearts.
Rapid adaptation of ATP formation and coronary flow is required when cardiac work is altered. Cardiac energy status was proposed to control both oxygen consumption (MVO2) and release of vasoactive adenosine (AR). To investigate the hypothesis of a linear relation between free AMP and AR, we employed 31P nuclear magnetic resonance (NMR) in a newly elaborated guinea pig heart performing pressure-volume work. Under basal conditions, MVO2 was 7.8 +/- 1.0 mumol.min-1.g-1, free AMP 297 +/- 189 nM and AR 226 +/- 179 pmol.min-1.g-1 (n = 29). Decreasing arterial PO2 by 50% reduced MVO2 and increased free AMP by 29%; however, AR rose threefold (n = 5). Doubling oxygen content of the perfusion medium (fluorocarbon emulsion) did not alter MVO2, free AMP, or AR (n = 6). When afterload was doubled, MVO2 increased (+45%) and AR decreased (-60%) despite no change in ADP or AMP (n = 6). Dobutamine increased MVO2 (+50%) and AMP (-98%); however, AR rose more than five times (n = 8). Switching substrates from glucose + pyruvate to glucose diminished MVO2 and increased ADP twofold and AMP fourfold, whereas AR remained constant (n = 6). Our findings demonstrate that cardiac energy status is also not the prime regulator of oxidative phosphorylation in the isolated heart. Changes in the oxygen supply-to-demand ratio induced a rise in AR that exceeded by far the increase in free AMP. Thus, additional factors, possibly inhibition of adenosine kinase, influence the release of vasoactive adenosine.
Decking
U K
UK
Institut für Herz und Kreislaufphysiologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Arens
S
S
Schlieper
G
G
Schulze
K
K
Schrader
J
J
D000241:Adenosine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002244:Carbon; D004280:Dobutamine / Q000494:pharmacology; D004734:Energy Metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D013379:Substrate Specificity
D000318:Adrenergic beta-Agonists; D004280:Dobutamine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D002244:Carbon; D000241:Adenosine; D010100:Oxygen