Temporal dynamics of inotropic, chronotropic, and metabolic responses during β1- and β2-AR stimulation in the isolated, perfused rat heart

P. McConville, R. G. Spencer, E. G. Lakatta

Research output: Contribution to journalArticlepeer-review

Abstract

During the β-adrenergic receptor (β-AR)-mediated stress response in the heart, the relations between functional responses and metabolism are ill defined, with the distinction between β1- and β2-AR subtypes creating further complexity. Specific outstanding questions include the temporal relation between inotropic and chronotropic responses and their metabolic correlates. We sought to elucidate the relative magnitudes and temporal dynamics of the response to β1- and β2-AR stimulation and the energy expenditure and bioenergetic state related to these responses in the isolated perfused rat heart. Inotropic [left ventricular developed pressure (LVDP) and dP/dr], chronotropic [heart rate (HR)], and metabolic responses were measured during β1- (n = 9; agonist: norepinephrine) and β2- (n = 9; agonist: zinterol) AR stimulation. Myocardial oxygen consumption (MV̇o2) was measured using fiberoptic oximetry, and high-energy phosphate levels and intracellular pH were measured using 31P NMR spectroscopy. A multiple-dose protocol was used, with near-maximal β-AR stimulation at the highest doses. In both β1 and β2 groups, there were dose-dependent increases in LVDP, dP/df, HR, and MV̇o2. The inotropic response showed more rapid onset, washout, and variation during dose than did the chronotropic response and was closely correlated with MV̇o2. This suggests that the myocardial bioenergetic state is more closely related to the inotropic response than to the chronotropic response. In addition, β1-AR stimulation resulted in a greater magnitude and rate of onset of inotropic and MV̇o2 responses than did β2-AR stimulation during maximal stimulation. However, a similar decrease in intracellular energy charge was seen in the two groups, consistent with a greater rate of oxidative phosphorylation during β1 than during β2-AR stimulation.

Original languageEnglish (US)
Pages (from-to)E412-E418
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume289
Issue number3 52-3
DOIs
StatePublished - Sep 2005
Externally publishedYes

Keywords

  • Adrenergic
  • Adrenergic receptor
  • Chronotropy
  • Inotropy
  • Metabolism
  • Myocardial oxygen consumption
  • Phosphorus-31 nuclear magnetic resonance
  • Rat heart
  • Receptors

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'Temporal dynamics of inotropic, chronotropic, and metabolic responses during β<sub>1</sub>- and β<sub>2</sub>-AR stimulation in the isolated, perfused rat heart'. Together they form a unique fingerprint.

Cite this