β-adrenergic and endothelin receptor interaction in dilated human cardiomyopathic myocardium

C. A. Walker, Adviye Ergul, A. Grubbs, M. R. Zile, J. L. Zellner, A. J. Crumbley, F. G. Spinale

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Although end-stage dilated cardiomyopathy (DCM) is characterized by defects in β-adrenergic receptor (β-AR) activity and increased endothelin-1 (ET-1), possible interactions between these 2 systems remain to be defined. Accordingly, the goal of this study was to determine the effects of ET receptor activation on β-AR signaling through measurement of cyclic adenosine monophosphate (cAMP) in normal and DCM myocardium. Methods and Results: Myocardial sarcolemmal preparations were prepared from normal human (n = 6), dilated cardiomyopathic (n = 10), and ischemic cardiomyopathic (ICM, n = 10) tissue. Basal cAMP production was measured in the presence of ET-1 alone (10−6 to 0−9 mol/L) as well as after (-)isoproterenol (10−6 to 10−2 mol/L) or forskolin (0.05 to 30.0 μmol/L) stimulation. β-AR and ET receptor profiles were determined by radiolabeled ligand assays. ET-1 inhibited basal cAMP production in all preparations in a concentration-dependent manner. However, β-AR-stimulated cAMP production by either isoproterenol or forskolin was not significantly affected by ET-1. β-AR receptor density was reduced, and a selective reduction of the ETB receptor occurred in both forms of DCM. Conclusions: Under basal conditions, ET receptor stimulation reduced cAMP levels, which may influence contractility, particularly with DCM.

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalJournal of Cardiac Failure
Volume7
Issue number2
DOIs
StatePublished - Jan 1 2001

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Endothelin Receptors
Cyclic AMP
Adrenergic Receptors
Dilated Cardiomyopathy
Endothelin-1
Myocardium
Colforsin
Isoproterenol
Ligands

Keywords

  • Congestive heart failure
  • Endothelin
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Walker, C. A., Ergul, A., Grubbs, A., Zile, M. R., Zellner, J. L., Crumbley, A. J., & Spinale, F. G. (2001). β-adrenergic and endothelin receptor interaction in dilated human cardiomyopathic myocardium. Journal of Cardiac Failure, 7(2), 129-137. https://doi.org/10.1054/jcaf.2001.24125

β-adrenergic and endothelin receptor interaction in dilated human cardiomyopathic myocardium. / Walker, C. A.; Ergul, Adviye; Grubbs, A.; Zile, M. R.; Zellner, J. L.; Crumbley, A. J.; Spinale, F. G.

In: Journal of Cardiac Failure, Vol. 7, No. 2, 01.01.2001, p. 129-137.

Research output: Contribution to journalArticle

Walker, CA, Ergul, A, Grubbs, A, Zile, MR, Zellner, JL, Crumbley, AJ & Spinale, FG 2001, 'β-adrenergic and endothelin receptor interaction in dilated human cardiomyopathic myocardium', Journal of Cardiac Failure, vol. 7, no. 2, pp. 129-137. https://doi.org/10.1054/jcaf.2001.24125
Walker, C. A. ; Ergul, Adviye ; Grubbs, A. ; Zile, M. R. ; Zellner, J. L. ; Crumbley, A. J. ; Spinale, F. G. / β-adrenergic and endothelin receptor interaction in dilated human cardiomyopathic myocardium. In: Journal of Cardiac Failure. 2001 ; Vol. 7, No. 2. pp. 129-137.
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