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Cardiovascular Research 2001 52(1):153-160; doi:10.1016/S0008-6363(01)00359-5
© 2001 by European Society of Cardiology
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Copyright © 2001, European Society of Cardiology

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

Tamas Habona,*, Eszter Szabadosa, Gabor Kesmarkya, Robert Halmosia, Tibor Pasta, Balazs Sumegib and Kalman Totha

aFirst Department of Medicine, Division of Cardiology, University of Pecs Medical School, Ifjusag u. 13, H-7634 Pecs, Hungary
bDepartment of Biochemistry, University of Pecs Medical School, Szigeti u. 12, H-7624 Pecs, Hungary

* Corresponding author. Tel.: +36-72-536-000; fax: +36-72-536-148 thabon{at}clinics.pote.hu

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. Conclusion: 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.

KEYWORDS CK, creatine kinase; DHR, dihydrorhodamine123; ECL, enhanced chemiluminescence; GOT, glutamate oxaloacetate transaminase; LDH, lactate dehydrogenase; MDA, malondialdehyde; NAD+, nicotinamide adenine dinucleotide (oxidized form); NADH, nicotinamide adenine dinucleotide (reduced form); PARP, poly(ADP-ribose) polymerase; PMS, phenazine methosulphate; RBC, red blood cell; ROS, reactive oxygen species


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