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

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

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 - 2001

Keywords

  • Congestive heart failure
  • Endothelin
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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