In vitro effect of carvedilol on professional phagocytes
Aim: 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-methionylleucylphenyl-alanine (fMLP, 0.1 mu mol/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 mu g/ml) stimulated). Results: Carvedilol (10 and 100 mu mol/l) significantly decreased opsonized zymosan- and fMPL-stimulated superoxide generation and myeloperoxidase release. Carvedilol (100 mu mol/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. Conclusion: 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. Copyright (c) 2007 S. Karger AG, Basel.