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Effects of carvedilol on oxidative stress in human endothelial cells and healthy volunteers

  • Pharmacodynamics
  • Published:
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Abstract

Objective

Carvedilol is a nonselective β- and α1-receptor antagonist with additional antioxidant properties in vitro. In this study, we assessed the antioxidative potential of carvedilol in cell culture and in antihypertensive doses in healthy men.

Methods

In vitro, human cultured endothelial cells were treated with native low-density lipoprotein (LDL), oxidized LDL or tumor necrosis factor (TNF)α in the absence and in the presence of carvedilol (40 µM); 8-iso-prostaglandin (PG)F2α, as parameter of oxidative stress, was determined in the supernatants. In a double-blind, randomized, cross-over study, 17 healthy men received 25 mg carvedilol b.i.d., 100 mg metoprolol b.i.d. or placebo for 6 days. After each treatment, systemic oxidative stress was assessed by measuring urinary excretion of 8-iso-PGF2α and 2,3-dinor-5,6-dihydro-8-iso-PGF2α, and the plasma concentration of 3-nitrotyrosine by means of gas chromatography-tandem mass spectrometry. In addition, thiobarbituric acid-reactive substances (TBARS) in plasma were assessed using spectrophotometry.

Results

Native LDL and oxidized LDL induced 8-iso-PGF2α production in endothelial cells. Carvedilol significantly reduced this effect (e.g., for oxidized LDL: 2.66±0.22 pg vs 1.46±0.14 pg 8-iso-PGF2α per µg protein, P<0.05). In healthy volunteers, carvedilol and metoprolol markedly decreased blood pressure and heart rate, but had no statistically significant effect on any indicator of oxidative stress measured. Remarkably, a trend toward reduction of urinary isoprostanes and 3-nitrotyrosine in plasma by both active treatments was observed, suggesting a non-specific antioxidative effect by β blockade.

Conclusions

In vitro, the antioxidative potential of carvedilol was confirmed. In healthy men, antihypertensive doses of carvedilol exert no specific inhibition of oxidative stress.

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Acknowledgements

We thank Mrs. B. Schubert and Mrs. I. Fuchs for their skillful technical assistance. The authors are indebted to L. Hoy, Ph.D., Department of Biometrics, Medizinische Hochschule Hannover, for statistical advice. This study was supported by an institutional grant by Hoffmann-La Roche, Grenzach-Wyhlen, Germany. The experiments in the study complied with the current laws of Germany.

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, Medizinische Hochschule Hannover, 30623 , Hannover, Germany

    Stefanie A. Fahlbusch, Dimitrios Tsikas, Christina Mehls, Frank-Mathias Gutzki, Jürgen C. Frölich & Dirk O. Stichtenoth

  2. Clinical Pharmacology Unit, Department of Pharmacology, Universitätsklinikum Hamburg-Eppendorf, 20246 , Hamburg, Germany

    Rainer H. Böger

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  1. Stefanie A. Fahlbusch
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  2. Dimitrios Tsikas
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Correspondence to Dirk O. Stichtenoth.

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Fahlbusch, S.A., Tsikas, D., Mehls, C. et al. Effects of carvedilol on oxidative stress in human endothelial cells and healthy volunteers. Eur J Clin Pharmacol 60, 83–88 (2004). https://doi.org/10.1007/s00228-004-0729-0

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  • DOI: https://doi.org/10.1007/s00228-004-0729-0

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