Adenosine and insulin mediate glucose uptake in normoxic rat hearts by different mechanisms.

The effect of adenosine (ADO) and its interaction with insulin (I) on myocardial glucose uptake was evaluated in the normoxic isolated rat heart using 2-[3H]deoxyglucose. Isovolumic hearts were perfused at constant flow with a nonrecirculating bicarbonate buffer containing 5.5 mM glucose as the sole substrate. After a 30-min equilibration period, the glucose and extracellular ([14C]sucrose) tracers were infused for 15 min before initiation of the 15-min experimental period. Both 100 microM ADO and 4 mU/ml I significantly increased glucose uptake (GU) compared with control values (in mumol.min-1 x g-1: ADO = 0.34 +/- 0.03, I = 0.44 +/- 0.03, control = 0.23 +/- 0.02; P < 0.05). In combination, ADO and I produced an additive increase in GU (0.54 +/- 0.03; P < 0.05 vs. control). The mechanism of enhanced GU by ADO and I was investigated with the glucose uptake inhibitors phloridzin (PZ) and phloretin (PT), each of which has a unique site of action on the cell membrane. ADO-mediated GU was completely blocked by 3 mM PZ (ADO + PZ = 0.20 +/- 0.01; P = NS vs. control), but I-stimulated GU was unaffected (I + PZ = 0.38 +/- 0.03; P = NS vs. I). Only GU attributable to ADO was blocked by PZ infused with ADO and I (ADO + I + PZ = 0.43 +/- 0.03; P = NS vs. I). Both ADO- and I-mediated GU were inhibited by 100 microM PT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine antagonism decreases metabolic but not functional recovery from ischemia.

The effect of adenosine receptor antagonism on function and metabolism was examined in isolated hearts during low flow ischemia and reperfusion. Isovolumic rat hearts perfused at constant flow were subjected to 30 min of ischemia followed by 30 min of reperfusion. Infusion of vehicle or 10 microM 8-phenyltheophylline (8-PT) was initiated 10 min before ischemia and maintained throughout reperfusion. 8-PT infusion had no significant effects on hemodynamic parameters or metabolism preischemia. During ischemia, left ventricular developed pressure declined to approximately 15% of preischemic values in control and 8-PT hearts, and ATP and PCr decreased to approximately 73 and 60% of preischemic values. Inorganic phosphate (Pi) increased to 353 = 41 and 424 +/- 53% of preischemic values in control and 8-PT hearts, respectively. After reperfusion, function recovered to greater than 95% of preischemic levels in control and 8-PT hearts. Unlike control hearts, recovery of metabolites was significantly different during reperfusion in 8-PT hearts (P less than 0.05); ATP, phosphocreatine, and Pi recovered to 82 +/- 8, 71 +/- 8, and 281 +/- 27% of preischemic values, respectively. Venous purine washout was significantly greater (P less than 0.05) during reperfusion in 8-PT hearts (327 +/- 113 nmol) than in control hearts (127 +/- 28 nmol). Blockade of adenosine receptors appears to adversely affect metabolic but not functional recovery in the ischemic-reperfused myocardium.