The effect of carvedilol on enhanced ADP-ribosylation and red blood cell membrane damage caused by free radicals

• Published in: Cardiovascular research 2001-10, Vol.52 (1), p.153-160
• Main Authors: HABON, Tamas, SZABADOS, Eszter, KESMARKY, Gabor, HALMOSI, Robert, PAST, Tibor, SUMEGI, Balazs, TOTH, Kalman
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate Ribose - metabolism; ADP Ribose Transferases; Adrenergic Antagonists - pharmacology; Animals; Biological and medical sciences; Blood Viscosity - drug effects; Carbazoles - pharmacology; Cardiovascular system; Carvedilol; Erythrocyte Membrane - metabolism; Hemorheology; Humans; Lipid Peroxidation - drug effects; Male; Medical sciences; Miscellaneous; Myocardial Reperfusion Injury - metabolism; NAD - metabolism; Perfusion; Pharmacology. Drug treatments; Poly(ADP-ribose) Polymerases - metabolism; Propanolamines - pharmacology; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(01)00359-5

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. 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. 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. 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.