[The effect of carvedilol on enhanced adp-ribosylation and red blood cell membrane damage caused by free radicals].
OBJECTIVE
Previous studies have reported that the beta and alpha adrenoceptor blocker carvedilol had unique protective effect on free radical induced myocardial injury. The aim of this study was to examine how carvedilol regulates ROI-mediated signaling and decreases RBC membrane damage in heart perfusion and rheological model.


METHODS
The ischemia-reperfusion induced oxidative cell damages, and changes in the intracellular signaling mediated by reactive oxygen species and peroxynitrite were studied on rats, in Langendorff heart 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-ribosylation. 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 PARP was also significantly inhibited by carvedilol.


CONCLUSIONS
Our results show that carvedilol can modulate the ROI-induced signaling through poly- and mono-ADP-ribosylation 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.
Habon
T
T
Pécsi Tudományegyetem, Altalános Orvostudományi Kar, I. Sz. Belgyógyászati Klinika, Kardiológiai Osztály. thabon@clinics.pote.hu
Szabados
E
E
Késmárky
G
G
Halmosi
R
R
Past
T
T
Sumegi
B
B
Tóth
K
K
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004910:Erythrocyte Membrane / Q000187:drug effects*; D005609:Free Radicals / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D005609:Free Radicals; D011412:Propanolamines; D000077261:Carvedilol; D000246:Adenosine Diphosphate Ribose