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

Tamas Habon, Eszter Szabados, Gabor Kesmarky, Robert Halmosi, Tibor Past, Balazs Sumegi, Kalman Toth

Research output: Contribution to journalArticle

21 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)153-160
Number of pages8
JournalCardiovascular research
Volume52
Issue number1
DOIs
Publication statusPublished - Sep 22 2001

Keywords

  • Free radicals
  • Ischemia
  • Microcirculation
  • Reperfusion
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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