Poly(ADP-ribose) polymerase inhibition reverses vascular dysfunction after {gamma}-irradiation

Journal Article · Tue Aug 01 04:00:00 EDT 2006 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2006.03.058· OSTI ID:20850038

Beller, Carsten J ^[1]; Radovits, Tamas ^[1]; Seres, Leila ^[1]; Kosse, Jens ^[1]; Krempien, Robert ^[2]; Gross, Marie-Luise ^[3]; Penzel, Roland ^[3]; Berger, Irina ^[3]; Huber, Peter E ^[4]; Hagl, Siegfried ^[1]; Szabo, Csaba ^[5]; Szabo, Gabor ^[1]

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1. Department of Cardiac Surgery, University of Heidelberg, Heidelberg (Germany)
2. Department of Clinical Radiology, University of Heidelberg, Heidelberg (Germany)
3. Department of Pathology, University of Heidelberg, Heidelberg (Germany)
4. Department of Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany)
5. Department of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest (Hungary)

Purpose: The generation of reactive oxygen species during {gamma}-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 {gamma}-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.

• OSTI ID: 20850038
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 65; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ACETYLCHOLINE
ADP
DNA DAMAGES
ENDOTHELIUM
ENZYMES
GAMMA RADIATION
INHIBITION
IRRADIATION
RIBOSE
VASOCONSTRICTION