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 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

Fingerprint

Adrenergic Receptors
Energy Metabolism
Pressure
Workload
Glycogenolysis
Oximetry
Oxidative Phosphorylation
Glycolysis
Acidosis
Oxygen Consumption
Phosphorus
Magnetic Resonance Spectroscopy
Heart Rate

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Differences in the bioenergetic response of the isolated perfused rat heart to selective β1- and β2-adrenergic receptor stimulation. / McConville, Patrick; Fishbein, Kenneth W.; Lakatta, Edward; Spencer, Richard G.S.

In: Circulation, Vol. 107, No. 16, 29.04.2003, p. 2146-2152.

Research output: Contribution to journalArticle

McConville, Patrick ; Fishbein, Kenneth W. ; Lakatta, Edward ; Spencer, Richard G.S. / Differences in the bioenergetic response of the isolated perfused rat heart to selective β1- and β2-adrenergic receptor stimulation. In: Circulation. 2003 ; Vol. 107, No. 16. pp. 2146-2152.
@article{720f5a41927f496985fcc3cdb61c5f27,
title = "Differences in the bioenergetic response of the isolated perfused rat heart to selective β1- and β2-adrenergic receptor stimulation",
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.",
keywords = "Imaging, Metabolism, Oxygen, Receptors, adrenergic, beta",
author = "Patrick McConville and Fishbein, {Kenneth W.} and Edward Lakatta and Spencer, {Richard G.S.}",
year = "2003",
month = "4",
day = "29",
doi = "10.1161/01.CIR.0000062686.72615.9B",
language = "English (US)",
volume = "107",
pages = "2146--2152",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "16",

}

TY - JOUR

T1 - Differences in the bioenergetic response of the isolated perfused rat heart to selective β1- and β2-adrenergic receptor stimulation

AU - McConville, Patrick

AU - Fishbein, Kenneth W.

AU - Lakatta, Edward

AU - Spencer, Richard G.S.

PY - 2003/4/29

Y1 - 2003/4/29

N2 - 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.

AB - 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.

KW - Imaging

KW - Metabolism

KW - Oxygen

KW - Receptors, adrenergic, beta

UR - http://www.scopus.com/inward/record.url?scp=0038755036&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038755036&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.0000062686.72615.9B

DO - 10.1161/01.CIR.0000062686.72615.9B

M3 - Article

C2 - 12707247

AN - SCOPUS:0038755036

VL - 107

SP - 2146

EP - 2152

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 16

ER -