Differences in the bioenergetic response of the isolated perfused rat heart to selective β1- and β2-adrenergic receptor stimulation

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

Research output: Contribution to journalArticle

Abstract

Background - In the heart, striking functional differences exist after stimulation of the β1- and β2-adrenergic receptor (AR) subtypes. These may be linked to differences in metabolic response during β1- and β2-AR stimulation. Methods and Results - The relation between work and metabolism was examined during selective β1- and β2-AR stimulation (β1 and β2 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 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 β1-AR (HCF, 475%; CP, 150%) than β2-AR (HCF, 90%; CP, 72%) stimulation, the relative decrease in the intracellular energy charge relative to baseline was similar for the β1 (HCF, 49%; CP, 64%) and β2 (HCF, 59%; CP, 55%) groups. For each group, an increase in oxygen consumption (MV̇o2) occurred commensurate with workload during HCF (β1, 141%; β2, 30%). During CP, however, the MV̇o2 increase was similar (β1, 39%; β2, 34%), despite the large RPP difference between the groups. During both protocols, there was greater acidosis during β1-AR than during β2-AR stimulation. Thus, at a given workload, intracellular energy charge decreased, and MV̇o2 (CP) increased to a greater extent during β2 than β1-AR stimulation. Conclusions - The bioenergetic differences are consistent with access to an additional substrate pool during β1-AR stimulation. This may occur via increased glycogenolysis during β1-AR stimulation, facilitating increased energy production by oxidative phosphorylation, and under flow-limiting conditions, anaerobic glycolysis.

Original languageEnglish (US)
Pages (from-to)2146-2152
Number of pages7
JournalCirculation
Volume107
Issue number16
DOIs
StatePublished - Apr 29 2003
Externally publishedYes

Keywords

  • Imaging
  • Metabolism
  • Oxygen
  • Receptors, adrenergic, beta

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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