PMID- 10692566
OWN - NLM
STAT- MEDLINE
DCOM- 20000328
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 59
IP  - 8
DP  - 2000 Apr 15
TI  - No effect of carvedilol on nitric oxide generation in phagocytes but modulation 
      of production of superoxide ions.
PG  - 1007-13
AB  - 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.
FAU - Asbrink, S
AU  - Asbrink S
AD  - Department of Medicine, The Center for Inflammation and Hematology Research, The 
      Clinical Research Center, Huddinge University Hospital, S-141 86, Huddinge, 
      Sweden.
FAU - Zickert, A
AU  - Zickert A
FAU - Bratt, J
AU  - Bratt J
FAU - Gyllenhammar, H
AU  - Gyllenhammar H
FAU - Palmblad, J
AU  - Palmblad J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Carbazoles)
RN  - 0 (Cytochrome c Group)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Propanolamines)
RN  - 0K47UL67F2 (Carvedilol)
RN  - 11062-77-4 (Superoxides)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antihypertensive Agents/pharmacology
MH  - Calcium/metabolism
MH  - Carbazoles/*pharmacology
MH  - Carvedilol
MH  - Chemotaxis, Leukocyte/drug effects
MH  - Cytochrome c Group/metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - GTP-Binding Proteins/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Mice
MH  - Neutrophils/*drug effects/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Oxidation-Reduction
MH  - Phagocytes/*drug effects/metabolism
MH  - Propanolamines/*pharmacology
MH  - Superoxides/*metabolism
MH  - Type C Phospholipases/metabolism
EDAT- 2000/02/29 09:00
MHDA- 2000/04/01 09:00
CRDT- 2000/02/29 09:00
PHST- 2000/02/29 09:00 [pubmed]
PHST- 2000/04/01 09:00 [medline]
PHST- 2000/02/29 09:00 [entrez]
AID - S0006-2952(99)00393-7 [pii]
AID - 10.1016/s0006-2952(99)00393-7 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2000 Apr 15;59(8):1007-13. doi: 10.1016/s0006-2952(99)00393-7.