title: The effect of carvedilol on enhanced ADP-ribosylation and red blood cell membrane damage caused by free radicals.
abstract: OBJECTIVE
  Previous studies have reported that the beta and alpha adrenoceptor blocker carvedilol has unique protective effects on free radical-induced myocardial injury. The aim of this study was to examine how carvedilol regulates reactive-oxygen-species-mediated signaling and decreases red blood cell membrane damage in heart perfusion and in a rheological model.
  
  
  METHODS
  The ischemia-reperfusion-induced oxidative cell damage, and changes in the intracellular signaling mediated by reactive oxygen species and peroxynitrite were studied on rat hearts in a Langendorff perfusion system (n=15). The effect of carvedilol on red blood cell suspension viscosity (hematocrit: 60%) incubated with free radical generator (phenazine methosulphate) was also investigated (n=10). The measurements were performed on a capillary viscosimeter.
  
  
  RESULTS
  In both studies a protective effect of carvedilol was found, as the decrease of red blood cell suspension viscosity and K(+) concentration in the supernatant indicated. Carvedilol significantly decreased the ischemia-reperfusion-induced free radical production and the NAD(+) catabolism and reversed the poly- and mono(ADP-ribosyl)ation. Carvedilol also decreased the lipid peroxidation and membrane damages as determined by free malondialdehyde production and the release of intracellular enzymes. The self ADP-ribosylation of isolated poly(ADP-ribose) polymerase was also significantly inhibited by carvedilol.
  
  
  CONCLUSIONS
  Our results show that carvedilol can modulate the reactive-oxygen-species-induced signaling through poly- and mono(ADP-ribosyl)ation reactions, the NAD(+) catabolism in postischemic perfused hearts and has a marked scavenger effect on free radical generator-induced red blood cell membrane damage. All these findings may play an important role in the beneficial effects of carvedilol treatment in different cardiovascular diseases.
authors.affiliation: First Department of Medicine, Division of Cardiology, University of Pecs Medical School, Ifjusag u. 13, H-7634, Pecs, Hungary. thabon@clinics.pote.hu
authors.forename: T
authors.initials: T
authors.lastname: Habon
authors.forename: E
authors.initials: E
authors.lastname: Szabados
authors.forename: G
authors.initials: G
authors.lastname: Kesmarky
authors.forename: R
authors.initials: R
authors.lastname: Halmosi
authors.forename: T
authors.initials: T
authors.lastname: Past
authors.forename: B
authors.initials: B
authors.lastname: Sumegi
authors.forename: K
authors.initials: K
authors.lastname: Toth
mesh_terms: D036002:ADP Ribose Transferases; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D001809:Blood Viscosity / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004910:Erythrocyte Membrane / Q000378:metabolism; D018056:Hemorheology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010477:Perfusion; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018674:Adrenergic Antagonists; D002227:Carbazoles; D011412:Propanolamines; D017382:Reactive Oxygen Species; D000077261:Carvedilol; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases