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Effects of adrenomedullin on human myocyte contractile function and beta-adrenergic response

Rupak Mukherjee1, M Marlina Multani, Jeffrey A Sample

  • 1Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.

Journal of Cardiovascular Pharmacology and Therapeutics
|December 20, 2002
PubMed

Insights

Adrenomedullin, a peptide known for vasodilation, was found to reduce contractility in human heart cells. It also negatively interacted with the beta-adrenergic system, impacting heart muscle function.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology

Background:

  • Adrenomedullin (ADM) is a peptide hormone known to induce systemic vasodilation.
  • Elevated plasma ADM levels are associated with cardiovascular diseases like heart failure.
  • While ADM receptors are present in the myocardium, its direct impact on human myocyte contractility was previously uncharacterized.

Purpose of the Study:

  • To investigate the direct effects of adrenomedullin on the contractility of isolated human left ventricular myocytes.
  • To explore the potential interaction between adrenomedullin and the beta-adrenergic receptor system in human cardiac myocytes.

Main Methods:

  • Human left ventricular myocytes were isolated from myocardial biopsies of patients undergoing coronary artery bypass surgery.
  • Myocyte shortening velocity was measured using videomicroscopy at baseline and after exposure to varying concentrations of adrenomedullin.
  • The effect of adrenomedullin on beta-adrenergic receptor-mediated contractility was assessed using isoproterenol.

Main Results:

  • Adrenomedullin significantly reduced myocyte shortening velocity in a dose-dependent manner.
  • The presence of adrenomedullin blunted the increase in myocyte shortening velocity induced by isoproterenol, indicating an interaction with the beta-adrenergic system.
  • These findings were observed in myocytes with normal left ventricular ejection fractions.

Conclusions:

  • Adrenomedullin exerts a negative inotropic effect on isolated human left ventricular myocytes.
  • Adrenomedullin negatively interacts with the beta-adrenergic receptor system, potentially modulating cardiac response to adrenergic stimulation.
  • This study reveals a dual role for adrenomedullin, causing systemic vasodilation while also reducing myocardial contractility.
Abstract

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