Metabolic correlates of adenosine formation in stimulated guinea pig heart.
Adenosine release into epicardial fluid and coronary effluent of isolated isovolumic guinea pig hearts was examined at baseline and after stimulation with norepinephrine (30 nM) during 31P-nuclear magnetic resonance spectroscopy to monitor myocardial metabolism. At baseline flow (9.6 +/- 0.3 ml.min-1.g-1), epicardial and venous adenosine concentrations were 154 +/- 40 and 17 +/- 5 nM, respectively. The phosphorylation potential (log[ATP]/[ADP][Pi]) and the phosphocreatine-inorganic phosphate ratio ([PCr]/[Pi]) were 5.26 +/- 0.04 and 8.5 +/- 0.7, respectively. Norepinephrine increased left ventricular pressure, heart rate, and myocardial O2 consumption rate by approximately 21, 70, and 45%, respectively, and increased epicardial and venous adenosine to 496 +/- 74 and 461 +/- 94 nM, respectively. Log-[ATP]/[ADP][Pi] and [PCr]/[Pi] declined to 4.57 +/- 0.06 and 1.9 +/- 0.3, respectively. Epicardial [AMP] increased from 54 +/- 13 to 123 +/- 24 nM. AMP was not detectable in the venous effluent. Coronary resistance correlated with epicardial and venous [adenosine] (r = 0.86 and 0.90). Epicardial and venous [adenosine] correlated with log[ATP]/[ADP][Pi], [PCr]/[Pi], and cytosolic [AMP]. Hence, interstitial adenosine is linked to cytosolic metabolism and may regulate coronary vascular resistance. Venous adenosine underestimates epicardial adenosine at baseline but more closely approximates epicardial adenosine during norepinephrine infusion.
Headrick
J P
JP
Department of Physiology, University of Virginia, Health Sciences Center, Charlottesville 22908.
Matherne
G P
GP
Berr
S S
SS
Han
D C
DC
Berne
R M
RM
D000241:Adenosine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes; D010766:Phosphorylation / Q000187:drug effects
D010759:Phosphorus Isotopes; D010725:Phosphocreatine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine; D010100:Oxygen; D009638:Norepinephrine