Response of failing canine and human heart cells to β2-adrenergic stimulation

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117 Scopus citations

Abstract

Background: Failing human hearts lose β1- but not β2-adrenergic receptors. In canine hearts with tachypacing failure, the ratio of β2- to β1-adrenergic receptors is increased. The present study was designed to determine whether heart failure increases sensitivity to β2-adrenergic stimulation in isolated canine ventricular cardiomyocytes and to verify that myocytes from failing human ventricles contain functional β2-adrenergic receptors. Methods and Results: Myocytes from healthy dogs, dogs with tachypacing failure, and human transplant recipients were loaded with fura 2- AM and subjected to electric field stimulation in the presence of zinterol, a highly selective β2-adrenergic agonist. Zinterol significantly increased [Ca2+](i) transient amplitudes in all three groups. The failing canine myocytes were significantly more responsive than normal to β2-adrenergic stimulation. We also measured isotonic twitches, indo-1 fluorescence transients, and L-type Ca2+ currents in healthy canine myocytes. Zinterol (10-5 mol/L) elicited large increases in the amplitudes of simultaneously recorded twitches and transients. Zinterol also increased L-type Ca2+ currents in the normal canine myocytes; this augmentation was abolished by 10-7 mol/L ICI 118,551. cAMP production by suspensions of healthy and failing canine myocytes was not increased by zinterol (10-9 to 10-5 mol/L), nor did 10-5 mol/L zinterol elicit phospholamban phosphorylation. Conclusions: Failing human ventricular cardiomyocytes contain functional β2-adrenergic receptors. Canine myocytes also contain functional β2- adrenergic receptors. The canine ventricular response to β2-agonists is increased in tachypacing failure. Positive inotropic responses to β2- stimulation are not mediated by increases in cAMP or cAMP-dependent phosphorylation of phospholamban.

Original languageEnglish (US)
Pages (from-to)1612-1618
Number of pages7
JournalCirculation
Volume92
Issue number6
DOIs
StatePublished - Sep 15 1995

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Keywords

  • calcium channels
  • cells
  • heart failure
  • myocardial contraction
  • receptors, adrenergic, beta
  • sarcoplasmic reticulum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Altschuld, R. A., Starling, R. C., Hamlin, R. L., Billman, G. E., Hensley, J., Castillo, L., Fertel, R. H., Hohl, C. M., Robitaille, P. M. L., Jones, L. R., Xiao, R. P., & Lakatta, E. G. (1995). Response of failing canine and human heart cells to β2-adrenergic stimulation. Circulation, 92(6), 1612-1618. https://doi.org/10.1161/01.CIR.92.6.1612