In vitro effect of carvedilol on professional phagocytes.
OBJECTIVE
Superfluous reactive nitrogen and oxygen species generation is implicated in the damage of tissues at sites of inflammation where activated neutrophils and macrophages are involved. This study was conducted to investigate whether the beneficial effects of carvedilol involve modulation of respiratory burst, degranulation-myeloperoxidase release and inducible nitric oxide synthase (iNOS) expression.


METHODS
Spectrophotometry and chemiluminescence were used to evaluate the effect of carvedilol on opsonized zymosan (0.5 mg/ml)- or N-formyl-methionyl-leucyl-phenyl-alanine (fMLP, 0.1 micromol/l)-stimulated superoxide generation and myeloperoxidase release in human neutrophils. Western blot analysis was used for iNOS expression and Griess reagent for nitric oxide production in RAW 264.7 macrophages (lipopolysaccharide (0.1 microg/ml) stimulated).


RESULTS
Carvedilol (10 and 100 micromol/l) significantly decreased opsonized zymosan- and fMPL-stimulated superoxide generation and myeloperoxidase release. Carvedilol (100 micromol/l) enhanced the effect of wortmannin (50 nmol/l), a specific inhibitor of 1-phosphatidylinositol 3-kinase and decreased iNOS expression and nitric oxide production.


CONCLUSIONS
Carvedilol appears to have a non-specific effect on membranes and to interfere with the phospholipase D signaling pathway, with subsequent inhibition of reactive oxygen species generation and myeloperoxidase release, without affecting iNOS expression.
Pecivová
Jana
J
Department of Cellular Pharmacology, Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Macicková
Tatiana
T
Lojek
Antonín
A
Gallova
Lucia
L
Cíz
Milan
M
Nosál'
Rado
R
Holománová
Dagmar
D
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D000077261:Carvedilol; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D049449:Luminescence; D008297:Male; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D009195:Peroxidase / Q000037:antagonists & inhibitors; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D013053:Spectrophotometry; D013481:Superoxides / Q000037:antagonists & inhibitors; D000077191:Wortmannin
D000730:Androstadienes; D002227:Carbazoles; D002317:Cardiovascular Agents; D011412:Propanolamines; D000077261:Carvedilol; D013481:Superoxides; D009569:Nitric Oxide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D000077191:Wortmannin