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Beta‐blockers reduce the release and synthesis of endothelin‐1 in human endothelial cells
Author(s) -
CD Garlichs,
H Zhang,
Andreas Mügge,
WG Daniel
Publication year - 1999
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.1999.00407.x
Subject(s) - celiprolol , propranolol , metoprolol , endothelins , endothelin receptor , pharmacology , endothelin 1 , medicine , atenolol , umbilical vein , endothelium , endocrinology , chemistry , receptor , in vitro , blood pressure , heart rate , biochemistry
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 β‐adrenergic antagonists. It is not known, however, whether this effect is caused by haemodynamic changes associated with the use of β‐adrenergic antagonists or by direct interaction of β‐blockers with human endothelial cells. The aim of this study was to determine whether β‐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 β‐blocker propranolol, the β 1 ‐blocker metoprolol and the β 1 ‐blocker and β 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 β‐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 β‐adrenergic antagonists on ET‐1 production of the endothelium may at least partially explain the efficacy of β‐blockers in the treatment of diseases such as advanced heart failure, essential hypertension as well as acute coronary syndromes.