Beta-blockers reduce the release and synthesis of endothelin-1 in human endothelial cells

Eur J Clin Invest. 1999 Jan;29(1):12-6. doi: 10.1046/j.1365-2362.1999.00407.x.


Background: Endothelins play an important role in cardiovascular diseases, and clinical trials have shown a reduction in endothelin levels after long-term treatment of chronic heart failure with beta-adrenergic antagonists. It is not known, however, whether this effect is caused by haemodynamic changes associated with the use of beta-adrenergic antagonists or by direct interaction of beta-blockers with human endothelial cells. The aim of this study was to determine whether beta-adrenergic antagonists have an influence on endothelin-1 (ET-1) synthesis and release in human endothelial cells.

Methods: Pretreatment of cultured endothelial cells from human umbilical veins (HUVECs) with different concentrations of the non-selective beta-blocker propranolol, the beta 1-blocker metoprolol and the beta 1-blocker and beta 2-agonist celiprolol (all 10(-7)-10(-4) mol L-1) was found to reduce ET-1 production. This ET-1-reducing effect was even more pronounced in thrombin-stimulated cells (10(-5) mol L-1 of propranolol, metoprolol and celiprolol: 19% +/- 5.8%, 25% +/- 4% and 37% +/- 5.2% respectively).

Results: Quantitative reverse transcriptase polymerase chain reaction and Northern blotting confirmed an inhibitory effect of the beta-blocker on biosynthesis. Furthermore, the ET-1-reducing effect of propranolol, metoprolol and celiprolol was not due to a compensatory increase in prostacyclin and was not reversible by N-nitro-L-arginine.

Conclusion: The effect of beta-adrenergic antagonists on ET-1 production of the endothelium may at least partially explain the efficacy of beta-blockers in the treatment of diseases such as advanced heart failure, essential hypertension as well as acute coronary syndromes.

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / analysis
  • Adrenergic beta-Antagonists / pharmacology*
  • Celiprolol / pharmacology
  • Cells, Cultured
  • Culture Media, Conditioned
  • Dose-Response Relationship, Drug
  • Endothelin-1 / metabolism*
  • Endothelins / analysis
  • Endothelins / genetics
  • Endothelium, Vascular / drug effects*
  • Humans
  • Metoprolol / pharmacology
  • Propanolamines / pharmacology*
  • Propranolol / pharmacology
  • Protein Precursors / analysis
  • Protein Precursors / genetics
  • RNA, Messenger / analysis
  • Thrombin / pharmacology


  • Adrenergic beta-Antagonists
  • Culture Media, Conditioned
  • Endothelin-1
  • Endothelins
  • Propanolamines
  • Protein Precursors
  • RNA, Messenger
  • 6-Ketoprostaglandin F1 alpha
  • Propranolol
  • Celiprolol
  • Thrombin
  • Metoprolol