Differences in the bioenergetic response of the isolated perfused rat heart to selective beta1- and beta2-adrenergic receptor stimulation.

BACKGROUND In the heart, striking functional differences exist after stimulation of the beta1- and beta2-adrenergic receptor (AR) subtypes. These may be linked to differences in metabolic response during beta1- and beta2-AR stimulation. METHODS AND RESULTS The relation between work and metabolism was examined during selective beta1- and beta2-AR stimulation (beta1 and beta2 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 beta1-AR (HCF, 475%; CP, 150%) than beta2-AR (HCF, 90%; CP, 72%) stimulation, the relative decrease in the intracellular energy charge relative to baseline was similar for the beta1 (HCF, 49%; CP, 64%) and beta2 (HCF, 59%; CP, 55%) groups. For each group, an increase in oxygen consumption (MVO2) occurred commensurate with workload during HCF (beta1, 141%; beta2, 30%). During CP, however, the MVO2 increase was similar (beta1, 39%; beta2, 34%), despite the large RPP difference between the groups. During both protocols, there was greater acidosis during beta1-AR than during beta2-AR stimulation. Thus, at a given workload, intracellular energy charge decreased, and MVO2 (CP) increased to a greater extent during beta2 than beta1-AR stimulation. CONCLUSIONS The bioenergetic differences are consistent with access to an additional substrate pool during beta1-AR stimulation. This may occur via increased glycogenolysis during beta1-AR stimulation, facilitating increased energy production by oxidative phosphorylation, and under flow-limiting conditions, anaerobic glycolysis.