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(Circulation. 2003;107:2146.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Differences in the Bioenergetic Response of the Isolated Perfused Rat Heart to Selective ß₁- and ß₂-Adrenergic Receptor Stimulation

Patrick McConville, PhD; Kenneth W. Fishbein, PhD; Edward G. Lakatta, MD; Richard G.S. Spencer, PhD, MD

From the NMR Unit, Laboratory of Clinical Investigation (P.M., K.W.F., R.G.S.S.), and Laboratory for Cardiovascular Science (P.M., E.G.L.), Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Md.

Correspondence to Dr Richard Spencer, NMR Unit, GRC, National Institute on Aging/NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224. E-mail spencer{at}helix.nih.gov

Background— In the heart, striking functional differences exist after stimulation of the ß₁- and ß₂-adrenergic receptor (AR) subtypes. These may be linked to differences in metabolic response during ß₁- and ß₂-AR stimulation.

Methods and Results— The relation between work and metabolism was examined during selective ß₁- and ß₂-AR stimulation (ß₁ and ß₂ 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 ß₁-AR (HCF, 475%; CP, 150%) than ß₂-AR (HCF, 90%; CP, 72%) stimulation, the relative decrease in the intracellular energy charge relative to baseline was similar for the ß₁ (HCF, 49%; CP, 64%) and ß₂ (HCF, 59%; CP, 55%) groups. For each group, an increase in oxygen consumption (MO₂) occurred commensurate with workload during HCF (ß₁, 141%; ß₂, 30%). During CP, however, the MO₂ increase was similar (ß₁, 39%; ß₂, 34%), despite the large RPP difference between the groups. During both protocols, there was greater acidosis during ß₁-AR than during ß₂-AR stimulation. Thus, at a given workload, intracellular energy charge decreased, and MO₂ (CP) increased to a greater extent during ß₂ than ß₁-AR stimulation.

Conclusions— The bioenergetic differences are consistent with access to an additional substrate pool during ß₁-AR stimulation. This may occur via increased glycogenolysis during ß₁-AR stimulation, facilitating increased energy production by oxidative phosphorylation, and under flow-limiting conditions, anaerobic glycolysis.

Key Words: receptors, adrenergic, beta • metabolism • oxygen • imaging

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