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 Szabo, Gábor Szabó

Research output: Contribution to journalArticle

9 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Poly Adenosine Diphosphate Ribose
ribose
adenosine diphosphate
Blood Vessels
Nitroprusside
irradiation
Acetylcholine
Phenylephrine
acetylcholine
Vasodilation
Enzyme Activation
Poly(ADP-ribose) Polymerases
sodium
Vasoconstrictor Agents
Vasoconstriction
DNA Damage
Endothelium
Aorta
Reactive Oxygen Species
vasoconstriction

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Poly(ADP-ribose) polymerase inhibition reverses vascular dysfunction after γ-irradiation. / Beller, Carsten J.; Radovits, Tamás; Seres, Leila; Kosse, Jens; Krempien, Robert; Gross, Marie Luise; Penzel, Roland; Berger, Irina; Huber, Peter E.; Hagl, Siegfried; Szabo, Csaba; Szabó, Gábor.

In: International Journal of Radiation Oncology Biology Physics, Vol. 65, No. 5, 01.08.2006, p. 1528-1535.

Research output: Contribution to journalArticle

Beller, CJ, Radovits, T, Seres, L, Kosse, J, Krempien, R, Gross, ML, Penzel, R, Berger, I, Huber, PE, Hagl, S, Szabo, C & Szabó, G 2006, 'Poly(ADP-ribose) polymerase inhibition reverses vascular dysfunction after γ-irradiation', International Journal of Radiation Oncology Biology Physics, vol. 65, no. 5, pp. 1528-1535. https://doi.org/10.1016/j.ijrobp.2006.03.058
Beller, Carsten J. ; Radovits, Tamás ; Seres, Leila ; Kosse, Jens ; Krempien, Robert ; Gross, Marie Luise ; Penzel, Roland ; Berger, Irina ; Huber, Peter E. ; Hagl, Siegfried ; Szabo, Csaba ; Szabó, Gábor. / Poly(ADP-ribose) polymerase inhibition reverses vascular dysfunction after γ-irradiation. In: International Journal of Radiation Oncology Biology Physics. 2006 ; Vol. 65, No. 5. pp. 1528-1535.
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AU - Seres, Leila

AU - Kosse, Jens

AU - Krempien, Robert

AU - Gross, Marie Luise

AU - Penzel, Roland

AU - Berger, Irina

AU - Huber, Peter E.

AU - Hagl, Siegfried

AU - Szabo, Csaba

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N2 - 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.

AB - 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.

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