On the antioxidant activity of carvedilol in human polymorphonuclear leukocytes in vitro and ex vivo.
OBJECTIVE
In the present study we investigated whether the beta-adrenoceptor antagonist carvedilol (CARV) [Dilatrend] prevented reactive oxygen metabolite (ROM) production in human polymorphonuclear leukocytes (PMNL) or interfered with ROM already generated. To specify the site of action of CARV, we evaluated its effect on extra- and intracellular ROM generation. In addition, we studied the effect of CARV therapy on ROM production in whole blood obtained from patients with congestive heart failure (CHF) combined with type II diabetes mellitus.


METHODS
ROM generation in whole blood and isolated PMNL was determined after phorbol 12-myristate-13-acetate (PMA-0.05 micromol/l) stimulation by luminol/isoluminol-enhanced chemiluminescence (CL) in the microplate luminometer Immunotech LM-01T.


RESULTS
CARV significantly decreased CL of human whole blood in the concentrations of 10, 20, 50 and 100 micromol/l, both when applied simultaneously and after stimulation. In isolated PMNL, CARV significantly decreased extracellular CL in the concentrations of 50 and 100 micromol/l, intracellular CL was decreased in the concentrations of 20, 50 and 100 micromol/l. The nonstimulated and PMA stimulated CL of whole blood was increased in patients before therapy in comparison with healthy controls. After CARV therapy, 25 mg/day and 50 mg/day, there was a trend to reduce CL as compared to values before therapy.


CONCLUSIONS
In human PMNL, CARV interfered in vitro and ex vivo with ROM generation as well as with already generated ROM, suggestive of its both "preventive" and "therapeutic" effect.
Drábiková
Katarína
K
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovakia. exfadrak@savba.sk
Jancinová
Viera
V
Nosál'
Radomír
R
Solík
Peter
P
Murín
Ján
J
Holománová
Dagmar
D
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D049449:Luminescence; D008165:Luminol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D000975:Antioxidants; D002227:Carbazoles; D011412:Propanolamines; D017382:Reactive Oxygen Species; D000077261:Carvedilol; D008165:Luminol; D013755:Tetradecanoylphorbol Acetate