Differences in the Bioenergetic Response of the Isolated Perfused Rat Heart to Selective

Background—In the heart, striking functional differences exist after stimulation of the 1and 2-adrenergic receptor (AR) subtypes. These may be linked to differences in metabolic response during 1and 2-AR stimulation. Methods and Results—The relation between work and metabolism was examined during selective 1and 2-AR stimulation ( 1 and 2 groups, respectively) in the isolated perfused rat heart. Measurements were made of rate-pressure product (RPP LV developed pressure heart rate), phosphorus-containing metabolites, and pH by P nuclear magnetic resonance spectroscopy and of O2 consumption by fiber-optic oximetry. Experiments were performed under high constant flow (HCF) and under flow-limiting conditions (constant pressure, CP). Despite substantially greater RPP increases relative to baseline during 1-AR (HCF, 475%; CP, 150%) than 2-AR (HCF, 90%; CP, 72%) stimulation, the relative decrease in the intracellular energy charge relative to baseline was similar for the 1 (HCF, 49%; CP, 64%) and 2 (HCF, 59%; CP, 55%) groups. For each group, an increase in oxygen consumption (MV̇O2) occurred commensurate with workload during HCF ( 1, 141%; 2, 30%). During CP, however, the MV̇O2 increase was similar ( 1, 39%; 2, 34%), despite the large RPP difference between the groups. During both protocols, there was greater acidosis during 1-AR than during 2-AR stimulation. Thus, at a given workload, intracellular energy charge decreased, and MV̇O2 (CP) increased to a greater extent during 2 than 1-AR stimulation. Conclusions—The bioenergetic differences are consistent with access to an additional substrate pool during 1-AR stimulation. This may occur via increased glycogenolysis during 1-AR stimulation, facilitating increased energy production by oxidative phosphorylation, and under flow-limiting conditions, anaerobic glycolysis. (Circulation. 2003; 107:2146-2152.)