No effect of carvedilol on nitric oxide generation in phagocytes but modulation of production of superoxide ions.
Since carvedilol has been claimed to possess antioxidative effects, this drug might affect functional responses, including nitric oxide (NO) generation, of polymorphonuclear neutrophils (PMN) and macrophages. When we assessed the effects of carvedilol on PMN responses in vitro, we observed that carvedilol dose dependently modulated generation of superoxide ions by NADPH oxidase when induced by the formylpeptide formyl-methionyl-leucyl-phenylalanine (fMLP) or the phorbol ester phorbol myristate acetate. This effect was not coupled to diminished phospholipase C activity. In contrast to the effect on NADPH oxidase, neither the fMLP-elicited NO generation by PMN nor the response of the murine macrophage cell line J774 to lipopolysaccharide was affected. There was no evidence from cell-free assay systems that carvedilol is a scavenger for superoxide ions or NO. Moreover, carvedilol did not affect other reactions dependent on NO, e.g. spontaneous or fMLP-stimulated PMN migration or lipoxin A(4)-, fMLP-, or A23187-induced neutrophil cytotoxicity for human umbilical vein endothelial cells. Thus, these effects point to the possibility that carvedilol modulates the NADPH oxidase of PMN but leaves the nitric oxide synthase of phagocytes intact.
Asbrink
S
S
Department of Medicine, The Center for Inflammation and Hematology Research, The Clinical Research Center, Huddinge University Hospital, S-141 86, Huddinge, Sweden.
Zickert
A
A
Bratt
J
J
Gyllenhammar
H
H
Palmblad
J
J
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003574:Cytochrome c Group / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D000959:Antihypertensive Agents; D002227:Carbazoles; D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D011412:Propanolamines; D000077261:Carvedilol; D013481:Superoxides; D009569:Nitric Oxide; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium