PMID- 15004731
OWN - NLM
STAT- MEDLINE
DCOM- 20040929
LR  - 20181130
IS  - 0031-6970 (Print)
IS  - 0031-6970 (Linking)
VI  - 60
IP  - 2
DP  - 2004 Apr
TI  - Effects of carvedilol on oxidative stress in human endothelial cells and healthy 
      volunteers.
PG  - 83-8
AB  - OBJECTIVE: Carvedilol is a nonselective beta- and alpha(1)-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)alpha in the absence and in the presence of carvedilol (40 micro M); 
      8-iso-prostaglandin (PG)F(2alpha), 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-PGF(2alpha) and 
      2,3-dinor-5,6-dihydro-8-iso-PGF(2alpha), 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-PGF(2alpha) 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-PGF(2alpha) per micro g 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 beta 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.
FAU - Fahlbusch, Stefanie A
AU  - Fahlbusch SA
AD  - Institute of Clinical Pharmacology, Medizinische Hochschule Hannover, 30623 
      Hannover, Germany.
FAU - Tsikas, Dimitrios
AU  - Tsikas D
FAU - Mehls, Christina
AU  - Mehls C
FAU - Gutzki, Frank-Mathias
AU  - Gutzki FM
FAU - Boger, Rainer H
AU  - Boger RH
FAU - Frolich, Jurgen C
AU  - Frolich JC
FAU - Stichtenoth, Dirk O
AU  - Stichtenoth DO
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20040305
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (2,3-dinor-5,6-dihydro-8-iso-prostaglandin F2(alpha))
RN  - 0 (Adrenergic Antagonists)
RN  - 0 (Antioxidants)
RN  - 0 (BM 910228)
RN  - 0 (Carbazoles)
RN  - 0 (Isoprostanes)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Propanolamines)
RN  - 0 (Reactive Nitrogen Species)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 0K47UL67F2 (Carvedilol)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - B7IN85G1HY (Dinoprost)
RN  - GEB06NHM23 (Metoprolol)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - W1ANC8Q5NW (8-isoprostaglandin E2)
SB  - IM
MH  - Adrenergic Antagonists/*pharmacology
MH  - Adult
MH  - Antioxidants/*pharmacology
MH  - Carbazoles/*pharmacology
MH  - Carvedilol
MH  - Cells, Cultured
MH  - Cross-Over Studies
MH  - Dinoprost/*analogs & derivatives/metabolism
MH  - Dinoprostone/*analogs & derivatives/metabolism
MH  - Double-Blind Method
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Isoprostanes/metabolism
MH  - Lipoproteins, LDL/pharmacology
MH  - Male
MH  - Metoprolol/pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Propanolamines/*pharmacology
MH  - Reactive Nitrogen Species/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Thiobarbituric Acid Reactive Substances/metabolism
MH  - Tyrosine/*analogs & derivatives/metabolism
EDAT- 2004/03/09 05:00
MHDA- 2004/09/30 05:00
CRDT- 2004/03/09 05:00
PHST- 2003/08/19 00:00 [received]
PHST- 2003/12/28 00:00 [accepted]
PHST- 2004/03/09 05:00 [pubmed]
PHST- 2004/09/30 05:00 [medline]
PHST- 2004/03/09 05:00 [entrez]
AID - 10.1007/s00228-004-0729-0 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2004 Apr;60(2):83-8. doi: 10.1007/s00228-004-0729-0. Epub 
      2004 Mar 5.