Background--In the heart, striking functional differences exist after stimulation of the ₁- and ₂-adrenergic receptor (AR) subtypes. These may be linked to differences in metabolic response during ₁- and ₂-AR stimulation.

Methods and Results--The relation between work and metabolism was examined during selective ₁- and 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 x heart rate), phosphorus-containing metabolites, and pH by ³¹P 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 (MVO₂) occurred commensurate with workload during HCF (₁, 141%; ₂, 30%). During CP, however, the MVO₂ 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 MVO₂ (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.