Poly(ADP-ribose) polymerase inhibition reverses vascular dysfunction after γ-irradiation

Carsten J. Beller, Tamás Radovits, Leila Seres, Jens Kosse, Robert Krempien, Marie Luise Gross, Roland Penzel, Irina Berger, Peter E. Huber, Siegfried Hagl, Csaba Szabó, Gábor Szabó

    Research output: Contribution to journalArticle

    9 Scopus citations

    Abstract

    Purpose: The generation of reactive oxygen species during γ-irradiation may induce DNA damage, leading to activation of the nuclear enzyme poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) culminating in endothelial dysfunction. In the present study, we assessed the effect of PARP inhibition on changes in vascular function after acute and short-term irradiation. Methods and Materials: In the acute experiments, aortic rings were exposed to 20 Gy of γ-irradiation. The aortae were harvested after 1 or 7 days. Two additional groups received the ultrapotent PARP inhibitor, INO-1001, for 1 or 7 days after irradiation. The aortic rings were precontracted by phenylephrine and relaxation to acetylcholine and sodium nitroprusside were studied. Results: The vasoconstrictor response to phenylephrine was significantly lower both acutely and 1 and 7 days after irradiation. Vasorelaxation to acetylcholine and sodium nitroprusside was not impaired acutely after irradiation. One and seven days after irradiation, vasorelaxation to acetylcholine and sodium nitroprusside was significantly enhanced. Treatment with INO-1001 reversed vascular dysfunction after irradiation. Conclusion: Vascular dysfunction was observed 1 and 7 days after irradiation, as evidenced by reduced vasoconstriction, coupled with endothelium-dependent and -independent hyperrelaxation. PARP inhibition restored vascular function and may, therefore, be suitable to reverse vascular dysfunction after irradiation.

    Original languageEnglish (US)
    Pages (from-to)1528-1535
    Number of pages8
    JournalInternational Journal of Radiation Oncology Biology Physics
    Volume65
    Issue number5
    DOIs
    StatePublished - Aug 1 2006

    Keywords

    • Aortic rings
    • PARP inhibition
    • Peroxynitrite
    • Vascular dysfunction
    • γ-Irradiation

    ASJC Scopus subject areas

    • Radiation
    • Oncology
    • Radiology Nuclear Medicine and imaging
    • Cancer Research

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  • Cite this

    Beller, C. J., Radovits, T., Seres, L., Kosse, J., Krempien, R., Gross, M. L., Penzel, R., Berger, I., Huber, P. E., Hagl, S., Szabó, C., & Szabó, G. (2006). Poly(ADP-ribose) polymerase inhibition reverses vascular dysfunction after γ-irradiation. International Journal of Radiation Oncology Biology Physics, 65(5), 1528-1535. https://doi.org/10.1016/j.ijrobp.2006.03.058